7-112002591-C-T

Variant names:

• chr7-112002591-C-T
• rs61159171
• NM_001363540.2:c.121+1457G>A

Variant summary

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

The NM_001363540.2(DOCK4):​c.121+1457G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,918 control chromosomes in the GnomAD database, including 11,872 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 0.39 (11872 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.121+1457G>A		intron_variant	Intron 2 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.121+1457G>A		intron_variant	Intron 2 of 52	5	NM_001363540.2	ENSP00000410746.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59394 AN: 151800 Hom.: 11851 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.391 AC: 59453 AN: 151918 Hom.: 11872 Cov.: 32 AF XY: 0.395 AC XY: 29341 AN XY: 74258

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.363

Alfa AF: 0.358 Hom.: 8217

Bravo AF: 0.388

Asia WGS AF: 0.400 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.71

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: rs61159171; hg19: chr7-111642646;