rs6791331

chr3-28264450-A-Cchr3-28264450-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMC1	NM_182523.2	c.109+1070A>C		intron_variant		ENST00000466830.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMC1	ENST00000466830.6	c.109+1070A>C		intron_variant		1	NM_182523.2	P1

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

Gnomad4 AFR AF: 0.995

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.971

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.8
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs6791331; hg19: chr3-28305941;