NM_001363540.2:c.1067-4088G>A

Variant names:

• chr7-111919992-C-T
• rs1014799
• NM_001363540.2:c.1067-4088G>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.1067-4088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,976 control chromosomes in the GnomAD database, including 4,483 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 0.24 (4483 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.1067-4088G>A		intron_variant	Intron 12 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.1067-4088G>A		intron_variant	Intron 12 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.1067-4088G>A		intron_variant	Intron 12 of 51	1		ENSP00000404179.1
DOCK4	ENST00000445943.5	c.1028-4088G>A		intron_variant	Intron 11 of 52	5		ENSP00000397412.1
DOCK4	ENST00000476846.5	n.1323-4088G>A		intron_variant	Intron 12 of 22	5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36954 AN: 151858 Hom.: 4484 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.243 AC: 36960 AN: 151976 Hom.: 4483 Cov.: 32 AF XY: 0.245 AC XY: 18211 AN XY: 74286

African (AFR) AF: 0.280 AC: 11596 AN: 41434

American (AMR) AF: 0.211 AC: 3218 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 605 AN: 3466

East Asian (EAS) AF: 0.353 AC: 1828 AN: 5176

South Asian (SAS) AF: 0.190 AC: 914 AN: 4808

European-Finnish (FIN) AF: 0.273 AC: 2885 AN: 10558

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15220 AN: 67958

Other (OTH) AF: 0.226 AC: 476 AN: 2106

Alfa AF: 0.231 Hom.: 900

Bravo AF: 0.241

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.63
PhyloP100		-0.046
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: rs1014799; hg19: chr7-111560047;