rs147438507

Variant names:

• chr2-62135936-A-G
• rs147438507
• NM_152516.4:c.568A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-62135936-A-G
• chr2-62135936-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_152516.4(COMMD1):​c.568A>G​(p.Asn190Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,533,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: COMMD1 NM_152516.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.340
• Publications: 1 publications found

Genes affected

COMMD1 (HGNC:23024): (copper metabolism domain containing 1) Enables several functions, including phosphatidylinositol-3,4-bisphosphate binding activity; phospholipid binding activity; and protein homodimerization activity. Involved in several processes, including Golgi to plasma membrane transport; negative regulation of protein localization to cell surface; and regulation of cellular protein metabolic process. Acts upstream of or within negative regulation of NF-kappaB transcription factor activity. Located in cytosol; endosome; and nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000229839 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07713142).
• BS2: High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152516.4. 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
	COMMD1	NM_152516.4	MANE Select	c.568A>G	p.Asn190Asp	missense	Exon 3 of 3	NP_689729.1	Q8N668-1
	COMMD1	NM_001321781.3		c.370A>G	p.Asn124Asp	missense	Exon 3 of 3	NP_001308710.1
	COMMD1	NM_001321782.3		c.370A>G	p.Asn124Asp	missense	Exon 3 of 3	NP_001308711.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COMMD1	ENST00000311832.6	TSL:1 MANE Select	c.568A>G	p.Asn190Asp	missense	Exon 3 of 3	ENSP00000308236.5	Q8N668-1
	ENSG00000229839	ENST00000425966.6	TSL:1	n.308+1613T>C		intron	N/A
	COMMD1	ENST00000897153.1		c.661A>G	p.Asn221Asp	missense	Exon 4 of 4	ENSP00000567212.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152214 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251330 AF XY: 0.0000294

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000224 AC: 31 AN: 1381412 Hom.: 0 Cov.: 22 AF XY: 0.0000202 AC XY: 14 AN XY: 692194

African (AFR) AF: 0.0000314 AC: 1 AN: 31850

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.00 AC: 0 AN: 84760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.0000289 AC: 30 AN: 1038530

Other (OTH) AF: 0.00 AC: 0 AN: 57748

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152214 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000659 Hom.: 0

Bravo AF: 0.0000416

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.34
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.048
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.078
MVP		0.50
MPC		0.47
ClinPred		0.28	T
GERP RS		3.2
PromoterAI		0.0064	Neutral
Varity_R		0.17
gMVP		0.25
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs147438507; hg19: chr2-62363071;