NM_001363540.2:c.5481+1646C>G

Variant names:

• chr7-111730580-G-C
• rs867915
• NM_001363540.2:c.5481+1646C>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.5481+1646C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,162 control chromosomes in the GnomAD database, including 181 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 0.045 (181 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0751 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	NM_001363540.2	MANE Select	c.5481+1646C>G		intron	N/A	NP_001350469.1	Q8N1I0-3
	DOCK4	NM_014705.4		c.5454+1646C>G		intron	N/A	NP_055520.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	ENST00000428084.6	TSL:5 MANE Select	c.5481+1646C>G		intron	N/A	ENSP00000410746.1	Q8N1I0-3
	DOCK4	ENST00000437633.6	TSL:1	c.5454+1646C>G		intron	N/A	ENSP00000404179.1	Q8N1I0-1
	DOCK4	ENST00000423057.6	TSL:1	c.3720+1646C>G		intron	N/A	ENSP00000412834.1	H0Y7H7

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6791 AN: 152044 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0446 AC: 6791 AN: 152162 Hom.: 181 Cov.: 32 AF XY: 0.0438 AC XY: 3261 AN XY: 74384

African (AFR) AF: 0.0609 AC: 2527 AN: 41500

American (AMR) AF: 0.0273 AC: 417 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3470

East Asian (EAS) AF: 0.0318 AC: 165 AN: 5182

South Asian (SAS) AF: 0.0817 AC: 394 AN: 4822

European-Finnish (FIN) AF: 0.0415 AC: 439 AN: 10586

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0388 AC: 2641 AN: 67988

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0416 Hom.: 18

Bravo AF: 0.0425

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.56
PhyloP100		-0.10
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: rs867915; hg19: chr7-111370636;