chr1-57870386-C-T

Variant names:

• chr1-57870386-C-T
• rs2038379
• NM_001379462.1:c.-211+13613G>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.-211+13613G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,808 control chromosomes in the GnomAD database, including 7,947 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 0.31 (7947 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 5 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-AS1 (HGNC:49443): (DAB1 antisense RNA 1)

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 (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-211+13613G>A		intron_variant	Intron 3 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-211+13613G>A		intron_variant	Intron 2 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-211+13613G>A		intron_variant	Intron 6 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-211+13613G>A		intron_variant	Intron 3 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1-AS1	ENST00000457412.6	n.66-6345C>T		intron_variant	Intron 1 of 3	5
DAB1	ENST00000477280.1	n.87+13613G>A		intron_variant	Intron 1 of 1	3
DAB1	ENST00000485760.5	n.551+13613G>A		intron_variant	Intron 6 of 20	2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47544 AN: 151690 Hom.: 7924 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.314 AC: 47609 AN: 151808 Hom.: 7947 Cov.: 32 AF XY: 0.313 AC XY: 23188 AN XY: 74194

African (AFR) AF: 0.424 AC: 17562 AN: 41388

American (AMR) AF: 0.363 AC: 5534 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1139 AN: 3458

East Asian (EAS) AF: 0.334 AC: 1714 AN: 5128

South Asian (SAS) AF: 0.272 AC: 1308 AN: 4808

European-Finnish (FIN) AF: 0.218 AC: 2304 AN: 10548

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17057 AN: 67932

Other (OTH) AF: 0.301 AC: 637 AN: 2114

Alfa AF: 0.276 Hom.: 13404

Bravo AF: 0.329

Asia WGS AF: 0.311 AC: 1084 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	0.41
DANN	Benign	0.42
PhyloP100		-1.2
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: rs2038379; hg19: chr1-58336058;