7-112077957-T-C

Variant names:

• chr7-112077957-T-C
• rs6959338
• NM_001363540.2:c.38-73826A>G

Variant summary

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

The NM_001363540.2(DOCK4):​c.38-73826A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,892 control chromosomes in the GnomAD database, including 22,684 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 0.52 (22684 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 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.38-73826A>G		intron	N/A	NP_001350469.1	Q8N1I0-3
	DOCK4	NM_014705.4		c.38-73826A>G		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.38-73826A>G		intron	N/A	ENSP00000410746.1	Q8N1I0-3
	DOCK4	ENST00000437633.6	TSL:1	c.38-73826A>G		intron	N/A	ENSP00000404179.1	Q8N1I0-1
	DOCK4	ENST00000476846.5	TSL:5	n.294-73826A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78684 AN: 151774 Hom.: 22647 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.519 AC: 78765 AN: 151892 Hom.: 22684 Cov.: 32 AF XY: 0.510 AC XY: 37862 AN XY: 74256

African (AFR) AF: 0.789 AC: 32675 AN: 41426

American (AMR) AF: 0.425 AC: 6482 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2065 AN: 5186

South Asian (SAS) AF: 0.348 AC: 1674 AN: 4814

European-Finnish (FIN) AF: 0.383 AC: 4035 AN: 10536

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 28978 AN: 67894

Other (OTH) AF: 0.467 AC: 984 AN: 2108

Alfa AF: 0.448 Hom.: 50116

Bravo AF: 0.530

Asia WGS AF: 0.390 AC: 1346 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.83
PhyloP100		-0.42
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: rs6959338; hg19: chr7-111718012;