20-32704020-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP6_Moderate BA1

The NM_053041.3(COMMD7):c.526+3G>A variant causes a splice donor 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. 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_donor_region, intron
• Scores: Splicing: ADA: 0.004853
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.36

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]

ACMG classification

Verdict is Benign. Variant got -11 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_single_submitter, 1 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/exons	MANE	UniProt
COMMD7	NM_053041.3	c.526+3G>A		splice_donor_region_variant, intron_variant		ENST00000278980.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COMMD7	ENST00000278980.11	c.526+3G>A		splice_donor_region_variant, intron_variant		1	NM_053041.3	P4
COMMD7	ENST00000446419.6	c.523+3G>A		splice_donor_region_variant, intron_variant		2		A1
COMMD7	ENST00000610160.1	c.*442G>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3280 AN: 152150 Hom.: 110 Cov.: 32

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

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

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

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 26, 2018

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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

Other links and lift over

dbSNP: rs61684036; hg19: chr20-31291822;