1-57011361-G-C

Position:

• chr1-57011361-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001365792.1(DAB1):​c.1445-89C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,469,518 control chromosomes in the GnomAD database, including 28,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (7847 hom., cov: 32)
  • Exomes 𝑓: 0.15 (20957 hom.)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.75

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]

LOC112267900 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 1-57011361-G-C is Benign according to our data. Variant chr1-57011361-G-C is described in ClinVar as [Benign]. Clinvar id is 1266639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAB1	NM_001365792.1	c.1445-89C>G		intron_variant		ENST00000371236.7
LOC112267900	XR_007066117.1	n.12029G>C		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAB1	ENST00000371236.7	c.1445-89C>G		intron_variant		5	NM_001365792.1	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40615 AN: 151954 Hom.: 7796 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.150 AC: 198241 AN: 1317446 Hom.: 20957 AF XY: 0.150 AC XY: 98475 AN XY: 655648

Gnomad4 AFR exome AF: 0.552

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.268 AC: 40733 AN: 152072 Hom.: 7847 Cov.: 32 AF XY: 0.272 AC XY: 20203 AN XY: 74348

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.235

Alfa AF: 0.0689 Hom.: 72

Bravo AF: 0.289

Asia WGS AF: 0.329 AC: 1140 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs697580; hg19: chr1-57477034;