3-28293336-G-T

Variant names:

• chr3-28293336-G-T
• rs1606388
• NM_182523.2:c.110-22997G>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.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
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMC1	NM_182523.2	MANE Select	c.110-22997G>T		intron	N/A	NP_872329.1
	CMC1	NM_001331185.2		c.242-22997G>T		intron	N/A	NP_001318114.1
	CMC1	NM_001331186.2		c.110-1098G>T		intron	N/A	NP_001318115.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMC1	ENST00000466830.6	TSL:1 MANE Select	c.110-22997G>T		intron	N/A	ENSP00000418348.1
	CMC1	ENST00000477739.1	TSL:1	n.320-22997G>T		intron	N/A
	CMC1	ENST00000423894.5	TSL:2	c.20-22997G>T		intron	N/A	ENSP00000404581.1

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

African (AFR) AF: 0.0784 AC: 3229 AN: 41168

American (AMR) AF: 0.221 AC: 3331 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1196 AN: 3464

East Asian (EAS) AF: 0.167 AC: 848 AN: 5090

South Asian (SAS) AF: 0.137 AC: 657 AN: 4788

European-Finnish (FIN) AF: 0.279 AC: 2808 AN: 10078

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.290 AC: 19617 AN: 67580

Other (OTH) AF: 0.233 AC: 487 AN: 2088

Alfa AF: 0.262 Hom.: 2984

Bravo AF: 0.209

Asia WGS AF: 0.156 AC: 538 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.76
PhyloP100		0.26
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: rs1606388; hg19: chr3-28334827;