rs17424216

Variant names:

• chr1-57379933-G-A
• rs17424216
• NM_001365792.1:c.-137+43997C>T

Variant summary

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

The NM_001365792.1(DAB1):​c.-137+43997C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,158 control chromosomes in the GnomAD database, including 5,409 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 0.26 (5409 hom., cov: 33)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365792.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	NM_001365792.1	MANE Select	c.-137+43997C>T		intron	N/A	NP_001352721.1
	DAB1	NM_001353983.2		c.-137+44686C>T		intron	N/A	NP_001340912.1
	DAB1	NM_001353985.2		c.-137+44261C>T		intron	N/A	NP_001340914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000371236.7	TSL:5 MANE Select	c.-137+43997C>T		intron	N/A	ENSP00000360280.1
	DAB1	ENST00000371230.1	TSL:5	c.-137+43997C>T		intron	N/A	ENSP00000360274.1
	DAB1	ENST00000485760.5	TSL:2	n.626-88767C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39103 AN: 152040 Hom.: 5402 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.257 AC: 39130 AN: 152158 Hom.: 5409 Cov.: 33 AF XY: 0.252 AC XY: 18758 AN XY: 74404

African (AFR) AF: 0.201 AC: 8348 AN: 41502

American (AMR) AF: 0.218 AC: 3329 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3468

East Asian (EAS) AF: 0.103 AC: 532 AN: 5180

South Asian (SAS) AF: 0.142 AC: 688 AN: 4830

European-Finnish (FIN) AF: 0.261 AC: 2755 AN: 10572

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21314 AN: 67998

Other (OTH) AF: 0.278 AC: 587 AN: 2108

Alfa AF: 0.296 Hom.: 6989

Bravo AF: 0.255

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17424216; hg19: chr1-57845605;