chr7-111857432-C-T

Variant names:

• chr7-111857432-C-T
• rs12113766
• NM_001363540.2:c.2473+5940G>A

Variant summary

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

The NM_001363540.2(DOCK4):​c.2473+5940G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,992 control chromosomes in the GnomAD database, including 8,704 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 0.34 (8704 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 0 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.2473+5940G>A		intron_variant	Intron 23 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.2473+5940G>A		intron_variant	Intron 23 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.2473+5940G>A		intron_variant	Intron 23 of 51	1		ENSP00000404179.1
DOCK4	ENST00000423057.6	c.826+5940G>A		intron_variant	Intron 7 of 35	1		ENSP00000412834.1
DOCK4	ENST00000445943.5	c.2434+5940G>A		intron_variant	Intron 22 of 52	5		ENSP00000397412.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51014 AN: 151874 Hom.: 8708 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.336 AC: 51030 AN: 151992 Hom.: 8704 Cov.: 32 AF XY: 0.333 AC XY: 24773 AN XY: 74300

African (AFR) AF: 0.391 AC: 16187 AN: 41440

American (AMR) AF: 0.332 AC: 5078 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 967 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1828 AN: 5170

South Asian (SAS) AF: 0.175 AC: 841 AN: 4818

European-Finnish (FIN) AF: 0.346 AC: 3651 AN: 10538

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21383 AN: 67966

Other (OTH) AF: 0.304 AC: 641 AN: 2108

Alfa AF: 0.334 Hom.: 1057

Bravo AF: 0.343

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.66
PhyloP100		-0.72
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: rs12113766; hg19: chr7-111497488;