rs7785891

chr7-112092516-C-G

Variant summary

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

The NM_001363540.2(DOCK4):c.38-88385G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,948 control chromosomes in the GnomAD database, including 10,336 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 0.36 (10336 hom., cov: 31)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK4	NM_001363540.2	c.38-88385G>C		intron_variant		ENST00000428084.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK4	ENST00000428084.6	c.38-88385G>C		intron_variant		5	NM_001363540.2	P3
DOCK4	ENST00000437633.6	c.38-88385G>C		intron_variant		1		A1
DOCK4	ENST00000476846.5	n.294-88385G>C		intron_variant, non_coding_transcript_variant		5
DOCK4	ENST00000661654.1	n.307-88385G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54380 AN: 151830 Hom.: 10336 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.00406

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.358 AC: 54409 AN: 151948 Hom.: 10336 Cov.: 31 AF XY: 0.351 AC XY: 26090 AN XY: 74250

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.00407

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.332

Alfa AF: 0.388 Hom.: 1493

Bravo AF: 0.344

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.9
Dann	Benign	0.70

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: rs7785891; hg19: chr7-111732571;