chr3-28264450-A-C

Variant names:

• chr3-28264450-A-C
• rs6791331
• NM_182523.2:c.109+1070A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182523.2(CMC1):​c.109+1070A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 152,310 control chromosomes in the GnomAD database, including 72,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.98 (72806 hom., cov: 32)
• Consequence: CMC1 NM_182523.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 1 publications found

Genes affected

CMC1 (HGNC:28783): (C-X9-C motif containing 1) Predicted to enable metal ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182523.2. 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
	CMC1	NM_182523.2	MANE Select	c.109+1070A>C		intron	N/A	NP_872329.1	Q7Z7K0
	CMC1	NM_001331185.2		c.241+1070A>C		intron	N/A	NP_001318114.1
	CMC1	NM_001331186.2		c.109+1070A>C		intron	N/A	NP_001318115.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMC1	ENST00000466830.6	TSL:1 MANE Select	c.109+1070A>C		intron	N/A	ENSP00000418348.1	Q7Z7K0
	CMC1	ENST00000477739.1	TSL:1	n.319+1070A>C		intron	N/A
	CMC1	ENST00000922195.1		c.241+1070A>C		intron	N/A	ENSP00000592254.1

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148783 AN: 152192 Hom.: 72745 Cov.: 32

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.971

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.978 AC: 148903 AN: 152310 Hom.: 72806 Cov.: 32 AF XY: 0.976 AC XY: 72660 AN XY: 74460

African (AFR) AF: 0.995 AC: 41375 AN: 41596

American (AMR) AF: 0.974 AC: 14878 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3378 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5191 AN: 5192

South Asian (SAS) AF: 0.988 AC: 4760 AN: 4820

European-Finnish (FIN) AF: 0.943 AC: 10003 AN: 10612

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66108 AN: 68026

Other (OTH) AF: 0.971 AC: 2053 AN: 2114

Alfa AF: 0.979 Hom.: 9197

Bravo AF: 0.981

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.84
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs6791331; hg19: chr3-28305941;