1-57027878-C-T

Variant names:

• chr1-57027878-C-T
• rs706363
• NM_001365792.1:c.724-1835G>A

Variant summary

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

The NM_001365792.1(DAB1):​c.724-1835G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,168 control chromosomes in the GnomAD database, including 54,147 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 0.84 (54147 hom., cov: 32)
• Consequence: DAB1 NM_001365792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952
• 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)

LOC105378748 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.897 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	NM_001365792.1	MANE Select	c.724-1835G>A		intron	N/A	NP_001352721.1	O75553-6
	DAB1	NM_001353983.2		c.724-1835G>A		intron	N/A	NP_001340912.1	O75553-6
	DAB1	NM_001353985.2		c.724-1835G>A		intron	N/A	NP_001340914.1	O75553-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000371236.7	TSL:5 MANE Select	c.724-1835G>A		intron	N/A	ENSP00000360280.1	O75553-6
	DAB1	ENST00000420954.6	TSL:1	c.718-1835G>A		intron	N/A	ENSP00000395296.2	O75553-5
	DAB1	ENST00000371231.5	TSL:5	c.823-1835G>A		intron	N/A	ENSP00000360275.1	O75553-1

Frequencies

GnomAD3 genomes AF: 0.842 AC: 128059 AN: 152050 Hom.: 54080 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.842 AC: 128187 AN: 152168 Hom.: 54147 Cov.: 32 AF XY: 0.841 AC XY: 62562 AN XY: 74382

African (AFR) AF: 0.779 AC: 32316 AN: 41496

American (AMR) AF: 0.909 AC: 13910 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3154 AN: 3470

East Asian (EAS) AF: 0.734 AC: 3792 AN: 5166

South Asian (SAS) AF: 0.836 AC: 4029 AN: 4818

European-Finnish (FIN) AF: 0.838 AC: 8879 AN: 10594

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59094 AN: 68010

Other (OTH) AF: 0.870 AC: 1835 AN: 2110

Alfa AF: 0.864 Hom.: 109062

Bravo AF: 0.846

Asia WGS AF: 0.796 AC: 2768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.076
DANN	Benign	0.17
PhyloP100		-0.95
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: rs706363; hg19: chr1-57493551;