1-57584467-C-T

Variant names:

• chr1-57584467-C-T
• rs10493230
• NM_001379462.1:c.-137+65125G>A

Variant summary

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

The NM_021080.5(DAB1):​c.-137+65125G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,104 control chromosomes in the GnomAD database, including 3,904 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 0.21 (3904 hom., cov: 32)
• Consequence: DAB1 NM_021080.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021080.5. 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_001379462.1		c.-137+65125G>A		intron	N/A	NP_001366391.1	O75553-6
	DAB1	NM_021080.5		c.-137+65125G>A		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-137+65125G>A		intron	N/A	NP_001366390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000485760.5	TSL:2	n.625+65125G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31935 AN: 151986 Hom.: 3902 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.210 AC: 31940 AN: 152104 Hom.: 3904 Cov.: 32 AF XY: 0.213 AC XY: 15845 AN XY: 74344

African (AFR) AF: 0.0783 AC: 3250 AN: 41526

American (AMR) AF: 0.216 AC: 3303 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5160

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4816

European-Finnish (FIN) AF: 0.281 AC: 2967 AN: 10576

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18207 AN: 67974

Other (OTH) AF: 0.219 AC: 462 AN: 2114

Alfa AF: 0.241 Hom.: 14986

Bravo AF: 0.199

Asia WGS AF: 0.255 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.29
PhyloP100		-0.21
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: rs10493230; hg19: chr1-58050139;