rs739617

Variant names:

• chr7-111870810-C-T
• rs739617
• NM_001363540.2:c.2028-1155G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363540.2. 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
	DOCK4	NM_001363540.2	MANE Select	c.2028-1155G>A		intron	N/A	NP_001350469.1	Q8N1I0-3
	DOCK4	NM_014705.4		c.2028-1155G>A		intron	N/A	NP_055520.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	ENST00000428084.6	TSL:5 MANE Select	c.2028-1155G>A		intron	N/A	ENSP00000410746.1	Q8N1I0-3
	DOCK4	ENST00000437633.6	TSL:1	c.2028-1155G>A		intron	N/A	ENSP00000404179.1	Q8N1I0-1
	DOCK4	ENST00000423057.6	TSL:1	c.381-1155G>A		intron	N/A	ENSP00000412834.1	H0Y7H7

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

African (AFR) AF: 0.114 AC: 4747 AN: 41508

American (AMR) AF: 0.184 AC: 2807 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3472

East Asian (EAS) AF: 0.145 AC: 749 AN: 5176

South Asian (SAS) AF: 0.114 AC: 549 AN: 4824

European-Finnish (FIN) AF: 0.201 AC: 2127 AN: 10576

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12317 AN: 67994

Other (OTH) AF: 0.141 AC: 299 AN: 2114

Alfa AF: 0.172 Hom.: 1348

Bravo AF: 0.161

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.082
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: rs739617; hg19: chr7-111510866;