7-111745028-G-T

Variant names:

• chr7-111745028-G-T
• rs718845
• NM_001363540.2:c.4677+1306C>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.4677+1306C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,036 control chromosomes in the GnomAD database, including 10,019 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 0.35 (10019 hom., cov: 31)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363540.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	NM_001363540.2	MANE Select	c.4677+1306C>A		intron	N/A	NP_001350469.1
	DOCK4	NM_014705.4		c.4650+1306C>A		intron	N/A	NP_055520.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	ENST00000428084.6	TSL:5 MANE Select	c.4677+1306C>A		intron	N/A	ENSP00000410746.1
	DOCK4	ENST00000437633.6	TSL:1	c.4650+1306C>A		intron	N/A	ENSP00000404179.1
	DOCK4	ENST00000423057.6	TSL:1	c.3030+1306C>A		intron	N/A	ENSP00000412834.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53818 AN: 151918 Hom.: 9992 Cov.: 31

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.355 AC: 53906 AN: 152036 Hom.: 10019 Cov.: 31 AF XY: 0.358 AC XY: 26650 AN XY: 74338

African (AFR) AF: 0.423 AC: 17562 AN: 41470

American (AMR) AF: 0.392 AC: 5996 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1616 AN: 5158

South Asian (SAS) AF: 0.541 AC: 2606 AN: 4818

European-Finnish (FIN) AF: 0.303 AC: 3202 AN: 10556

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20409 AN: 67960

Other (OTH) AF: 0.367 AC: 776 AN: 2114

Alfa AF: 0.304 Hom.: 5071

Bravo AF: 0.361

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.40
PhyloP100		0.12
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: rs718845; hg19: chr7-111385084;