rs11706542

Variant names:

• chr3-28287092-C-T
• rs11706542
• NM_182523.2:c.109+23712C>T

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+23712C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,000 control chromosomes in the GnomAD database, including 4,451 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 0.23 (4451 hom., cov: 32)
• Consequence: CMC1 NM_182523.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.999
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMC1	NM_182523.2	c.109+23712C>T		intron_variant	Intron 2 of 3	ENST00000466830.6	NP_872329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMC1	ENST00000466830.6	c.109+23712C>T		intron_variant	Intron 2 of 3	1	NM_182523.2	ENSP00000418348.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34828 AN: 151882 Hom.: 4448 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.229 AC: 34860 AN: 152000 Hom.: 4451 Cov.: 32 AF XY: 0.227 AC XY: 16854 AN XY: 74284

African (AFR) AF: 0.120 AC: 4989 AN: 41492

American (AMR) AF: 0.229 AC: 3495 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1197 AN: 3464

East Asian (EAS) AF: 0.168 AC: 868 AN: 5168

South Asian (SAS) AF: 0.139 AC: 670 AN: 4822

European-Finnish (FIN) AF: 0.288 AC: 3035 AN: 10532

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19793 AN: 67922

Other (OTH) AF: 0.245 AC: 518 AN: 2114

Alfa AF: 0.262 Hom.: 4128

Bravo AF: 0.224

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.67
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11706542; hg19: chr3-28328583;