NM_001379462.1:c.-375+31839C>T

Variant names:

• chr1-57938951-G-A
• rs1202773
• NM_001379462.1:c.-375+31839C>T

Variant summary

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

The NM_001379462.1(DAB1):​c.-375+31839C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,786 control chromosomes in the GnomAD database, including 3,146 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 0.17 (3146 hom., cov: 31)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAB1	NM_001379462.1	c.-375+31839C>T		intron_variant	Intron 2 of 17		NP_001366391.1
DAB1	NM_021080.5	c.-374-54789C>T		intron_variant	Intron 1 of 16		NP_066566.3
DAB1	NM_001379461.1	c.-374-54789C>T		intron_variant	Intron 5 of 20		NP_001366390.1
DAB1	NM_001353980.2	c.-375+31839C>T		intron_variant	Intron 2 of 5		NP_001340909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAB1	ENST00000485760.5	n.388-54789C>T		intron_variant	Intron 5 of 20	2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25123 AN: 151668 Hom.: 3139 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.166 AC: 25173 AN: 151786 Hom.: 3146 Cov.: 31 AF XY: 0.165 AC XY: 12241 AN XY: 74156

African (AFR) AF: 0.349 AC: 14429 AN: 41302

American (AMR) AF: 0.0777 AC: 1185 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3468

East Asian (EAS) AF: 0.125 AC: 642 AN: 5150

South Asian (SAS) AF: 0.114 AC: 548 AN: 4806

European-Finnish (FIN) AF: 0.130 AC: 1368 AN: 10518

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0908 AC: 6172 AN: 67974

Other (OTH) AF: 0.130 AC: 273 AN: 2108

Alfa AF: 0.127 Hom.: 451

Bravo AF: 0.169

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.73
DANN	Benign	0.73
PhyloP100		-0.98
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: rs1202773; hg19: chr1-58404623;