20-32704020-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBA1

The NM_053041.3(COMMD7):​c.526+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,613,748 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 110 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 113 hom. )

Consequence

COMMD7
NM_053041.3 splice_region, intron

Scores

2
Splicing: ADA: 0.004853
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.36
Variant links:
Genes affected
COMMD7 (HGNC:16223): (COMM domain containing 7) Enables NF-kappaB binding activity. Involved in negative regulation of NF-kappaB transcription factor activity; negative regulation of transcription, DNA-templated; and tumor necrosis factor-mediated signaling pathway. Predicted to be located in cytoplasmic vesicle. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.15).
BP6
Variant 20-32704020-C-T is Benign according to our data. Variant chr20-32704020-C-T is described in ClinVar as [Benign]. Clinvar id is 777539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0731 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COMMD7NM_053041.3 linkc.526+3G>A splice_region_variant, intron_variant Intron 8 of 8 ENST00000278980.11 NP_444269.2 Q86VX2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COMMD7ENST00000278980.11 linkc.526+3G>A splice_region_variant, intron_variant Intron 8 of 8 1 NM_053041.3 ENSP00000278980.6 Q86VX2-1
ENSG00000285382ENST00000646357.1 linkc.526+3G>A splice_region_variant, intron_variant Intron 8 of 8 ENSP00000493768.1 A0A2R8Y455

Frequencies

GnomAD3 genomes
AF:
0.0216
AC:
3280
AN:
152150
Hom.:
110
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0752
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00825
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.0134
GnomAD3 exomes
AF:
0.00563
AC:
1401
AN:
249056
Hom.:
43
AF XY:
0.00423
AC XY:
571
AN XY:
135112
show subpopulations
Gnomad AFR exome
AF:
0.0793
Gnomad AMR exome
AF:
0.00383
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000263
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00331
GnomAD4 exome
AF:
0.00213
AC:
3110
AN:
1461480
Hom.:
113
Cov.:
33
AF XY:
0.00179
AC XY:
1298
AN XY:
727010
show subpopulations
Gnomad4 AFR exome
AF:
0.0753
Gnomad4 AMR exome
AF:
0.00428
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000450
Gnomad4 OTH exome
AF:
0.00532
GnomAD4 genome
AF:
0.0216
AC:
3294
AN:
152268
Hom.:
110
Cov.:
32
AF XY:
0.0216
AC XY:
1605
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0753
Gnomad4 AMR
AF:
0.00818
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.0132
Alfa
AF:
0.0110
Hom.:
16
Bravo
AF:
0.0240
Asia WGS
AF:
0.00520
AC:
19
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 26, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.15
CADD
Benign
22
DANN
Benign
0.97
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0049
dbscSNV1_RF
Benign
0.060
SpliceAI score (max)
0.010
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: rs61684036; hg19: chr20-31291822; API