rs370081454

Variant names:

• chr20-32704472-C-A
• rs370081454
• NM_053041.3:c.445G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-32704472-C-A
• chr20-32704472-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_053041.3(COMMD7):​c.445G>T​(p.Glu149*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000686 in 1,458,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: COMMD7 NM_053041.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.445G>T	p.Glu149*	stop_gained	Exon 7 of 9	NP_444269.2	Q86VX2-1
	COMMD7	NM_001099339.2		c.442G>T	p.Glu148*	stop_gained	Exon 7 of 9	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.445G>T	p.Glu149*	stop_gained	Exon 7 of 9	ENSP00000278980.6	Q86VX2-1
	ENSG00000285382	ENST00000646357.1		c.445G>T	p.Glu149*	stop_gained	Exon 7 of 9	ENSP00000493768.1	A0A2R8Y455
	COMMD7	ENST00000855720.1		c.445G>T	p.Glu149*	stop_gained	Exon 7 of 9	ENSP00000525779.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458332 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725492

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110514

Other (OTH) AF: 0.00 AC: 0 AN: 60270

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		5.6
Vest4		0.43
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=66/134	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs370081454; hg19: chr20-31292274;