rs6687842

Variant names:

• chr1-57350260-C-A
• rs6687842
• NM_001365792.1:c.-136-59094G>T

Variant summary

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

The NM_001365792.1(DAB1):​c.-136-59094G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,966 control chromosomes in the GnomAD database, including 13,707 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 0.42 (13707 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001365792.1	c.-136-59094G>T		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.-136-59094G>T		intron_variant	Intron 1 of 14	5	NM_001365792.1	ENSP00000360280.1
DAB1	ENST00000371230.1	c.-136-59094G>T		intron_variant	Intron 1 of 6	5		ENSP00000360274.1
DAB1	ENST00000485760.5	n.626-59094G>T		intron_variant	Intron 7 of 20	2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63430 AN: 151848 Hom.: 13697 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.418 AC: 63478 AN: 151966 Hom.: 13707 Cov.: 32 AF XY: 0.410 AC XY: 30428 AN XY: 74292

African (AFR) AF: 0.454 AC: 18821 AN: 41428

American (AMR) AF: 0.385 AC: 5888 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3470

East Asian (EAS) AF: 0.110 AC: 568 AN: 5162

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4814

European-Finnish (FIN) AF: 0.389 AC: 4105 AN: 10562

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29867 AN: 67938

Other (OTH) AF: 0.426 AC: 897 AN: 2108

Alfa AF: 0.347 Hom.: 1381

Bravo AF: 0.425

Asia WGS AF: 0.172 AC: 599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.55
PhyloP100		-0.058
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: rs6687842; hg19: chr1-57815932; COSMIC: COSV64680467;