rs11706542

Positions:

• chr3-28287092-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• 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/exons	MANE	UniProt
CMC1	NM_182523.2	c.109+23712C>T		intron_variant		ENST00000466830.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMC1	ENST00000466830.6	c.109+23712C>T		intron_variant		1	NM_182523.2	P1

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

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.245

Alfa AF: 0.264 Hom.: 2996

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11706542; hg19: chr3-28328583;