chr7-111870907-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001363540.2(DOCK4):​c.2027+1083T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,014 control chromosomes in the GnomAD database, including 3,483 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 0.21 ( 3483 hom., cov: 32)

Consequence

DOCK4
NM_001363540.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.293
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DOCK4NM_001363540.2 linkuse as main transcriptc.2027+1083T>A intron_variant ENST00000428084.6 NP_001350469.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DOCK4ENST00000428084.6 linkuse as main transcriptc.2027+1083T>A intron_variant 5 NM_001363540.2 ENSP00000410746 P3Q8N1I0-3

Frequencies

GnomAD3 genomes
AF:
0.207
AC:
31462
AN:
151896
Hom.:
3475
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.272
Gnomad AMI
AF:
0.265
Gnomad AMR
AF:
0.204
Gnomad ASJ
AF:
0.166
Gnomad EAS
AF:
0.148
Gnomad SAS
AF:
0.138
Gnomad FIN
AF:
0.199
Gnomad MID
AF:
0.101
Gnomad NFE
AF:
0.182
Gnomad OTH
AF:
0.183
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.207
AC:
31497
AN:
152014
Hom.:
3483
Cov.:
32
AF XY:
0.207
AC XY:
15354
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.273
Gnomad4 AMR
AF:
0.204
Gnomad4 ASJ
AF:
0.166
Gnomad4 EAS
AF:
0.147
Gnomad4 SAS
AF:
0.138
Gnomad4 FIN
AF:
0.199
Gnomad4 NFE
AF:
0.182
Gnomad4 OTH
AF:
0.180
Alfa
AF:
0.206
Hom.:
422
Bravo
AF:
0.214
Asia WGS
AF:
0.115
AC:
400
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
5.6
DANN
Benign
0.81

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17158926; hg19: chr7-111510963; API