rs1476517

Variant names:

• chr7-111857770-G-A
• rs1476517
• NM_001363540.2:c.2473+5602C>T

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+5602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,932 control chromosomes in the GnomAD database, including 7,803 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 0.32 (7803 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.2473+5602C>T		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+5602C>T		intron_variant	Intron 23 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.2473+5602C>T		intron_variant	Intron 23 of 51	1		ENSP00000404179.1
DOCK4	ENST00000423057.6	c.826+5602C>T		intron_variant	Intron 7 of 35	1		ENSP00000412834.1
DOCK4	ENST00000445943.5	c.2434+5602C>T		intron_variant	Intron 22 of 52	5		ENSP00000397412.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48446 AN: 151814 Hom.: 7810 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.319 AC: 48459 AN: 151932 Hom.: 7803 Cov.: 32 AF XY: 0.317 AC XY: 23537 AN XY: 74250

African (AFR) AF: 0.335 AC: 13896 AN: 41426

American (AMR) AF: 0.325 AC: 4968 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3472

East Asian (EAS) AF: 0.350 AC: 1803 AN: 5146

South Asian (SAS) AF: 0.152 AC: 732 AN: 4810

European-Finnish (FIN) AF: 0.347 AC: 3659 AN: 10534

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21367 AN: 67960

Other (OTH) AF: 0.290 AC: 610 AN: 2104

Alfa AF: 0.313 Hom.: 20818

Bravo AF: 0.324

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.95
PhyloP100		-0.89
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: rs1476517; hg19: chr7-111497826;