rs4110981

Variant names:

• chr1-58046377-T-C
• rs4110981
• NM_001379462.1:c.-450-75512A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-58046377-T-C
• chr1-58046377-T-G

Variant summary

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

The NM_001379462.1(DAB1):​c.-450-75512A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,010 control chromosomes in the GnomAD database, including 14,769 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 0.43 (14769 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 3 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 (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-450-75512A>G		intron_variant	Intron 1 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-374-162215A>G		intron_variant	Intron 1 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-375+104134A>G		intron_variant	Intron 5 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-450-75512A>G		intron_variant	Intron 1 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.387+104134A>G		intron_variant	Intron 5 of 20	2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65549 AN: 151892 Hom.: 14767 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.431 AC: 65570 AN: 152010 Hom.: 14769 Cov.: 32 AF XY: 0.428 AC XY: 31789 AN XY: 74302

African (AFR) AF: 0.337 AC: 13972 AN: 41450

American (AMR) AF: 0.428 AC: 6530 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1559 AN: 3462

East Asian (EAS) AF: 0.187 AC: 967 AN: 5170

South Asian (SAS) AF: 0.275 AC: 1324 AN: 4822

European-Finnish (FIN) AF: 0.525 AC: 5545 AN: 10562

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34150 AN: 67958

Other (OTH) AF: 0.403 AC: 851 AN: 2112

Alfa AF: 0.474 Hom.: 72571

Bravo AF: 0.425

Asia WGS AF: 0.222 AC: 773 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.51
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: rs4110981; hg19: chr1-58512049; COSMIC: COSV64717995;