1-57069525-C-A

Variant names:

• chr1-57069525-C-A
• rs3738556
• NM_001365792.1:c.598-100G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365792.1(DAB1):​c.598-100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 954,090 control chromosomes in the GnomAD database, including 25,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4291 hom., cov: 32)
  • Exomes 𝑓: 0.21 (20989 hom.)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22
• Publications: 8 publications found

Genes affected

DAB1 (HGNC:2661): (DAB adaptor protein 1) The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. [provided by RefSeq, Jan 2017]

DAB1 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 37

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-57069525-C-A is Benign according to our data. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-57069525-C-A is described in CliVar as Benign. Clinvar id is 1257976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.598-100G>T		intron_variant	Intron 7 of 14	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.598-100G>T		intron_variant	Intron 7 of 14	5	NM_001365792.1	ENSP00000360280.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33897 AN: 151910 Hom.: 4290 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.209 AC: 167366 AN: 802062 Hom.: 20989 AF XY: 0.208 AC XY: 87789 AN XY: 422218

African (AFR) AF: 0.234 AC: 4679 AN: 19972

American (AMR) AF: 0.430 AC: 16209 AN: 37730

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 3723 AN: 20936

East Asian (EAS) AF: 0.493 AC: 17562 AN: 35614

South Asian (SAS) AF: 0.252 AC: 17448 AN: 69176

European-Finnish (FIN) AF: 0.231 AC: 10346 AN: 44752

Middle Eastern (MID) AF: 0.148 AC: 651 AN: 4402

European-Non Finnish (NFE) AF: 0.167 AC: 88970 AN: 531360

Other (OTH) AF: 0.204 AC: 7778 AN: 38120

GnomAD4 genome AF: 0.223 AC: 33923 AN: 152028 Hom.: 4291 Cov.: 32 AF XY: 0.230 AC XY: 17052 AN XY: 74296

African (AFR) AF: 0.246 AC: 10181 AN: 41456

American (AMR) AF: 0.327 AC: 4991 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3472

East Asian (EAS) AF: 0.481 AC: 2478 AN: 5154

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4822

European-Finnish (FIN) AF: 0.246 AC: 2592 AN: 10534

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11173 AN: 67994

Other (OTH) AF: 0.202 AC: 426 AN: 2112

Alfa AF: 0.161 Hom.: 562

Bravo AF: 0.232

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.60
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3738556; hg19: chr1-57535198;