NM_053041.3:c.526+3G>A

Variant names:

• chr20-32704020-C-T
• rs61684036
• NM_053041.3:c.526+3G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

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: Splicing: ADA: 0.004853
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.36
• Publications: 1 publications found

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]

ENSG00000285382 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053041.3. 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
	COMMD7	NM_053041.3	MANE Select	c.526+3G>A		splice_region intron	N/A	NP_444269.2	Q86VX2-1
	COMMD7	NM_001099339.2		c.523+3G>A		splice_region intron	N/A	NP_001092809.1	Q86VX2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD7	ENST00000278980.11	TSL:1 MANE Select	c.526+3G>A		splice_region intron	N/A	ENSP00000278980.6	Q86VX2-1
	ENSG00000285382	ENST00000646357.1		c.526+3G>A		splice_region intron	N/A	ENSP00000493768.1	A0A2R8Y455
	COMMD7	ENST00000855720.1		c.478-54G>A		intron	N/A	ENSP00000525779.1

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

GnomAD2 exomes AF: 0.00563 AC: 1401 AN: 249056 AF XY: 0.00423

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 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

African (AFR) AF: 0.0753 AC: 2521 AN: 33472

American (AMR) AF: 0.00428 AC: 191 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000163 AC: 14 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1111892

Other (OTH) AF: 0.00532 AC: 321 AN: 60384

GnomAD4 genome AF: 0.0216 AC: 3294 AN: 152268 Hom.: 110 Cov.: 32 AF XY: 0.0216 AC XY: 1605 AN XY: 74462

African (AFR) AF: 0.0753 AC: 3129 AN: 41536

American (AMR) AF: 0.00818 AC: 125 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0195 Hom.: 56

Bravo AF: 0.0240

Asia WGS AF: 0.00520 AC: 19 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Benign	0.97
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=76/24	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61684036; hg19: chr20-31291822;