chr7-111747683-A-G

Position:

• chr7-111747683-A-G

Variant summary

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

The NM_001363540.2(DOCK4):​c.4417-240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,988 control chromosomes in the GnomAD database, including 33,468 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 0.66 (33468 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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 (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.4417-240T>C		intron_variant		ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.4417-240T>C		intron_variant		5	NM_001363540.2	ENSP00000410746.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100011 AN: 151870 Hom.: 33463 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.658 AC: 100043 AN: 151988 Hom.: 33468 Cov.: 32 AF XY: 0.651 AC XY: 48361 AN XY: 74282

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.645

Alfa AF: 0.677 Hom.: 15921

Bravo AF: 0.653

Asia WGS AF: 0.454 AC: 1579 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	0.99
DANN	Benign	0.78

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: rs1859025; hg19: chr7-111387739;