rs1606388

Positions:

• chr3-28293336-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182523.2(CMC1):​c.110-22997G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 150,554 control chromosomes in the GnomAD database, including 4,205 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 0.22 (4205 hom., cov: 30)
• Consequence: CMC1 NM_182523.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260

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]

CMC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMC1	NM_182523.2	c.110-22997G>T		intron_variant		ENST00000466830.6	NP_872329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMC1	ENST00000466830.6	c.110-22997G>T		intron_variant		1	NM_182523.2	ENSP00000418348.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32444 AN: 150444 Hom.: 4202 Cov.: 30

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.216 AC: 32469 AN: 150554 Hom.: 4205 Cov.: 30 AF XY: 0.213 AC XY: 15624 AN XY: 73444

Gnomad4 AFR AF: 0.0784

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.233

Alfa AF: 0.261 Hom.: 2660

Bravo AF: 0.209

Asia WGS AF: 0.156 AC: 538 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.76

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: rs1606388; hg19: chr3-28334827;