1-57609613-C-T

Variant names:

• chr1-57609613-C-T
• rs1935046
• NM_001379462.1:c.-137+39979G>A

Variant summary

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

The NM_001379462.1(DAB1):​c.-137+39979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,290 control chromosomes in the GnomAD database, including 65,995 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 0.93 (65995 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-137+39979G>A		intron_variant	Intron 4 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-137+39979G>A		intron_variant	Intron 3 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-137+39979G>A		intron_variant	Intron 7 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-137+39979G>A		intron_variant	Intron 4 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.625+39979G>A		intron_variant	Intron 7 of 20	2

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141263 AN: 152172 Hom.: 65952 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.943

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

GnomAD4 genome AF: 0.928 AC: 141366 AN: 152290 Hom.: 65995 Cov.: 32 AF XY: 0.930 AC XY: 69263 AN XY: 74464

African (AFR) AF: 0.811 AC: 33709 AN: 41540

American (AMR) AF: 0.963 AC: 14735 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3304 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 0.978 AC: 4724 AN: 4828

European-Finnish (FIN) AF: 0.973 AC: 10337 AN: 10624

Middle Eastern (MID) AF: 0.983 AC: 287 AN: 292

European-Non Finnish (NFE) AF: 0.973 AC: 66189 AN: 68032

Other (OTH) AF: 0.943 AC: 1991 AN: 2112

Alfa AF: 0.949 Hom.: 14919

Bravo AF: 0.923

Asia WGS AF: 0.980 AC: 3407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.82
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1935046; hg19: chr1-58075285;