7-112077957-T-C

Position:

• chr7-112077957-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.38-73826A>G		intron_variant		ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.38-73826A>G		intron_variant		5	NM_001363540.2	ENSP00000410746	P3
DOCK4	ENST00000437633.6	c.38-73826A>G		intron_variant		1		ENSP00000404179	A1
DOCK4	ENST00000476846.5	n.294-73826A>G		intron_variant, non_coding_transcript_variant		5
DOCK4	ENST00000661654.1	n.307-73826A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.467

Alfa AF: 0.425 Hom.: 18897

Bravo AF: 0.530

Asia WGS AF: 0.390 AC: 1346 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.83

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: rs6959338; hg19: chr7-111718012;