rs739617

chr7-111870810-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363540.2(DOCK4):c.2028-1155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,148 control chromosomes in the GnomAD database, including 2,086 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 0.16 (2086 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

Genes affected

DOCK4 (HGNC:19192): (dedicator of cytokinesis 4) This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK4	NM_001363540.2	c.2028-1155G>A		intron_variant		ENST00000428084.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK4	ENST00000428084.6	c.2028-1155G>A		intron_variant		5	NM_001363540.2	P3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24444 AN: 152030 Hom.: 2087 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.161 AC: 24443 AN: 152148 Hom.: 2086 Cov.: 32 AF XY: 0.161 AC XY: 12004 AN XY: 74382

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.141

Alfa AF: 0.172 Hom.: 1201

Bravo AF: 0.161

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	11
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs739617; hg19: chr7-111510866;