rs944923

Variant names:

• chr1-57014751-C-G
• rs944923
• NM_001365792.1:c.1444+132G>C

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.1444+132G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 626,808 control chromosomes in the GnomAD database, including 17,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (7861 hom., cov: 33)
  • Exomes 𝑓: 0.17 (9374 hom.)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.51
• Publications: 0 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)

LOC112267900 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-57014751-C-G is Benign according to our data. Variant chr1-57014751-C-G is described in ClinVar as Benign. ClinVar VariationId is 1235828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365792.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	NM_001365792.1	MANE Select	c.1444+132G>C		intron	N/A	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.1444+132G>C		intron	N/A	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.1444+132G>C		intron	N/A	NP_001340914.1	O75553-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000371236.7	TSL:5 MANE Select	c.1444+132G>C		intron	N/A	ENSP00000360280.1	O75553-6
	DAB1	ENST00000420954.6	TSL:1	c.1438+132G>C		intron	N/A	ENSP00000395296.2	O75553-5
	DAB1	ENST00000371231.5	TSL:5	c.1543+132G>C		intron	N/A	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40620 AN: 151904 Hom.: 7809 Cov.: 33

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.166 AC: 78738 AN: 474786 Hom.: 9374 AF XY: 0.165 AC XY: 39910 AN XY: 241338

African (AFR) AF: 0.539 AC: 6681 AN: 12384

American (AMR) AF: 0.358 AC: 4559 AN: 12722

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 1356 AN: 12730

East Asian (EAS) AF: 0.401 AC: 11466 AN: 28624

South Asian (SAS) AF: 0.234 AC: 6239 AN: 26622

European-Finnish (FIN) AF: 0.190 AC: 7196 AN: 37798

Middle Eastern (MID) AF: 0.181 AC: 353 AN: 1952

European-Non Finnish (NFE) AF: 0.114 AC: 36122 AN: 316272

Other (OTH) AF: 0.186 AC: 4766 AN: 25682

GnomAD4 genome AF: 0.268 AC: 40738 AN: 152022 Hom.: 7861 Cov.: 33 AF XY: 0.272 AC XY: 20217 AN XY: 74308

African (AFR) AF: 0.534 AC: 22114 AN: 41418

American (AMR) AF: 0.322 AC: 4912 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1714 AN: 5174

South Asian (SAS) AF: 0.240 AC: 1156 AN: 4810

European-Finnish (FIN) AF: 0.197 AC: 2078 AN: 10558

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7737 AN: 68012

Other (OTH) AF: 0.234 AC: 494 AN: 2108

Alfa AF: 0.203 Hom.: 613

Bravo AF: 0.288

Asia WGS AF: 0.331 AC: 1147 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.092
DANN	Benign	0.34
PhyloP100		-1.5
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: rs944923; hg19: chr1-57480424;