rs11207007

Variant names:

• chr1-57327683-C-T
• rs11207007
• NM_001365792.1:c.-136-36517G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365792.1(DAB1):​c.-136-36517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,936 control chromosomes in the GnomAD database, including 10,072 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10072 hom., cov: 31)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.-136-36517G>A		intron_variant	Intron 1 of 14	ENST00000371236.7	NP_001352721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000371236.7	c.-136-36517G>A		intron_variant	Intron 1 of 14	5	NM_001365792.1	ENSP00000360280.1
DAB1	ENST00000371230.1	c.-136-36517G>A		intron_variant	Intron 1 of 6	5		ENSP00000360274.1
DAB1	ENST00000485760.5	n.626-36517G>A		intron_variant	Intron 7 of 20	2

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52787 AN: 151818 Hom.: 10074 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52799 AN: 151936 Hom.: 10072 Cov.: 31 AF XY: 0.342 AC XY: 25363 AN XY: 74264

African (AFR) AF: 0.222 AC: 9208 AN: 41464

American (AMR) AF: 0.350 AC: 5348 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3468

East Asian (EAS) AF: 0.115 AC: 591 AN: 5152

South Asian (SAS) AF: 0.208 AC: 998 AN: 4802

European-Finnish (FIN) AF: 0.388 AC: 4093 AN: 10544

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29612 AN: 67928

Other (OTH) AF: 0.363 AC: 765 AN: 2110

Alfa AF: 0.375 Hom.: 2071

Bravo AF: 0.343

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.065
DANN	Benign	0.28
PhyloP100		-2.5
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: rs11207007; hg19: chr1-57793355; COSMIC: COSV64680407;