7-111839068-C-T

Variant names:

• chr7-111839068-C-T
• rs7783121
• NM_001363540.2:c.2737-4382G>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.2737-4382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,028 control chromosomes in the GnomAD database, including 11,583 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 0.33 (11583 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.2737-4382G>A		intron_variant	Intron 25 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.2737-4382G>A		intron_variant	Intron 25 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.2737-4382G>A		intron_variant	Intron 25 of 51	1		ENSP00000404179.1
DOCK4	ENST00000423057.6	c.1090-4382G>A		intron_variant	Intron 9 of 35	1		ENSP00000412834.1
DOCK4	ENST00000445943.5	c.2805+1695G>A		intron_variant	Intron 25 of 52	5		ENSP00000397412.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50663 AN: 151908 Hom.: 11556 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.334 AC: 50752 AN: 152028 Hom.: 11583 Cov.: 32 AF XY: 0.330 AC XY: 24550 AN XY: 74328

African (AFR) AF: 0.653 AC: 27067 AN: 41456

American (AMR) AF: 0.226 AC: 3451 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3466

East Asian (EAS) AF: 0.354 AC: 1831 AN: 5172

South Asian (SAS) AF: 0.134 AC: 648 AN: 4822

European-Finnish (FIN) AF: 0.254 AC: 2686 AN: 10562

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.196 AC: 13325 AN: 67960

Other (OTH) AF: 0.309 AC: 653 AN: 2110

Alfa AF: 0.226 Hom.: 3019

Bravo AF: 0.352

Asia WGS AF: 0.257 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.77
PhyloP100		-0.84
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: rs7783121; hg19: chr7-111479124;