NM_001379462.1:c.-211+54961G>T

Variant names:

• chr1-57829038-C-A
• rs852778
• NM_001379462.1:c.-211+54961G>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.-211+54961G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,874 control chromosomes in the GnomAD database, including 27,786 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 0.60 (27786 hom., cov: 32)
• Consequence: DAB1 NM_001379462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379462.1. 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_001379462.1		c.-211+54961G>T		intron	N/A	NP_001366391.1	O75553-6
	DAB1	NM_021080.5		c.-211+54961G>T		intron	N/A	NP_066566.3
	DAB1	NM_001379461.1		c.-211+54961G>T		intron	N/A	NP_001366390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAB1	ENST00000477280.1	TSL:3	n.88-2583G>T		intron	N/A
	DAB1	ENST00000485760.5	TSL:2	n.551+54961G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91349 AN: 151756 Hom.: 27733 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.602 AC: 91449 AN: 151874 Hom.: 27786 Cov.: 32 AF XY: 0.602 AC XY: 44658 AN XY: 74206

African (AFR) AF: 0.676 AC: 27999 AN: 41422

American (AMR) AF: 0.649 AC: 9905 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1880 AN: 3462

East Asian (EAS) AF: 0.578 AC: 2973 AN: 5148

South Asian (SAS) AF: 0.492 AC: 2369 AN: 4812

European-Finnish (FIN) AF: 0.588 AC: 6201 AN: 10540

Middle Eastern (MID) AF: 0.593 AC: 172 AN: 290

European-Non Finnish (NFE) AF: 0.563 AC: 38235 AN: 67914

Other (OTH) AF: 0.568 AC: 1199 AN: 2110

Alfa AF: 0.491 Hom.: 1587

Bravo AF: 0.613

Asia WGS AF: 0.538 AC: 1869 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.6
DANN	Benign	0.45
PhyloP100		2.1
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: rs852778; hg19: chr1-58294710;