chr7-112079789-A-C

Variant names:

• chr7-112079789-A-C
• rs10487338
• NM_001363540.2:c.38-75658T>G

Variant summary

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

The NM_001363540.2(DOCK4):​c.38-75658T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,254 control chromosomes in the GnomAD database, including 880 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 0.079 (880 hom., cov: 33)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.38-75658T>G		intron_variant	Intron 1 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.38-75658T>G		intron_variant	Intron 1 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.38-75658T>G		intron_variant	Intron 1 of 51	1		ENSP00000404179.1
DOCK4	ENST00000476846.5	n.294-75658T>G		intron_variant	Intron 1 of 22	5
DOCK4	ENST00000661654.1	n.307-75658T>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0788 AC: 11990 AN: 152136 Hom.: 882 Cov.: 33

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0508

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0784

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

GnomAD4 genome AF: 0.0787 AC: 11987 AN: 152254 Hom.: 880 Cov.: 33 AF XY: 0.0819 AC XY: 6101 AN XY: 74452

African (AFR) AF: 0.0784 AC: 3258 AN: 41572

American (AMR) AF: 0.146 AC: 2227 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0508 AC: 176 AN: 3466

East Asian (EAS) AF: 0.397 AC: 2055 AN: 5172

South Asian (SAS) AF: 0.148 AC: 716 AN: 4828

European-Finnish (FIN) AF: 0.0334 AC: 355 AN: 10618

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0441 AC: 3000 AN: 67994

Other (OTH) AF: 0.0785 AC: 166 AN: 2114

Alfa AF: 0.0570 Hom.: 51

Bravo AF: 0.0878

Asia WGS AF: 0.245 AC: 853 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.45
PhyloP100		1.3
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: rs10487338; hg19: chr7-111719844;