1-57311710-T-G

Variant names:

• chr1-57311710-T-G
• rs632935
• NM_001365792.1:c.-136-20544A>C

Variant summary

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

The NM_001365792.1(DAB1):​c.-136-20544A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,978 control chromosomes in the GnomAD database, including 22,347 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 0.54 (22347 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 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.-136-20544A>C		intron	N/A	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.-136-20544A>C		intron	N/A	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.-136-20544A>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.-136-20544A>C		intron	N/A	ENSP00000360280.1	O75553-6
	DAB1	ENST00000959331.1		c.-136-20544A>C		intron	N/A	ENSP00000629390.1
	DAB1	ENST00000853968.1		c.-136-20544A>C		intron	N/A	ENSP00000524027.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81241 AN: 151860 Hom.: 22308 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.535 AC: 81339 AN: 151978 Hom.: 22347 Cov.: 32 AF XY: 0.536 AC XY: 39840 AN XY: 74300

African (AFR) AF: 0.619 AC: 25651 AN: 41432

American (AMR) AF: 0.662 AC: 10118 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3470

East Asian (EAS) AF: 0.531 AC: 2737 AN: 5150

South Asian (SAS) AF: 0.469 AC: 2257 AN: 4810

European-Finnish (FIN) AF: 0.449 AC: 4743 AN: 10558

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32437 AN: 67958

Other (OTH) AF: 0.544 AC: 1148 AN: 2110

Alfa AF: 0.513 Hom.: 7410

Bravo AF: 0.559

Asia WGS AF: 0.498 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.76
PhyloP100		0.17
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: rs632935; hg19: chr1-57777382; COSMIC: COSV107467971; COSMIC: COSV107467971;