rs4255455

Variant names:

• chr10-126920416-A-C
• rs4255455
• NM_001290223.2:c.46+14853A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-126920416-A-C
• chr10-126920416-A-G
• chr10-126920416-A-T

Variant summary

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

The NM_001290223.2(DOCK1):​c.46+14853A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,084 control chromosomes in the GnomAD database, including 18,412 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 0.48 (18412 hom., cov: 33)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224
• Publications: 1 publications found

Genes affected

DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ENSG00000305416 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.46+14853A>C		intron_variant	Intron 1 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.46+14853A>C		intron_variant	Intron 1 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.46+14853A>C		intron_variant	Intron 1 of 51	1		ENSP00000280333.6
ENSG00000305416	ENST00000810815.1	n.*104A>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73032 AN: 151966 Hom.: 18389 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.481 AC: 73115 AN: 152084 Hom.: 18412 Cov.: 33 AF XY: 0.479 AC XY: 35602 AN XY: 74342

African (AFR) AF: 0.589 AC: 24417 AN: 41482

American (AMR) AF: 0.590 AC: 9016 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1569 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2543 AN: 5158

South Asian (SAS) AF: 0.605 AC: 2913 AN: 4814

European-Finnish (FIN) AF: 0.291 AC: 3079 AN: 10576

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28168 AN: 67978

Other (OTH) AF: 0.503 AC: 1063 AN: 2112

Alfa AF: 0.439 Hom.: 44683

Bravo AF: 0.507

Asia WGS AF: 0.565 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.29
PhyloP100		0.22
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: rs4255455; hg19: chr10-128608985;