rs2002059

Variant names:

• chr10-99371098-A-G
• rs2002059
• NM_020348.3:c.2177-5957A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020348.3(CNNM1):​c.2177-5957A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 152,210 control chromosomes in the GnomAD database, including 1,026 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 0.097 (1026 hom., cov: 32)
• Consequence: CNNM1 NM_020348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• Publications: 2 publications found

Genes affected

CNNM1 (HGNC:102): (cyclin and CBS domain divalent metal cation transport mediator 1) This gene encodes a member of the ancient conserved domain protein family. The encoded protein may bind copper. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM1	NM_020348.3	c.2177-5957A>G		intron_variant	Intron 6 of 10	ENST00000356713.5	NP_065081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM1	ENST00000356713.5	c.2177-5957A>G		intron_variant	Intron 6 of 10	1	NM_020348.3	ENSP00000349147.4
CNNM1	ENST00000696687.1	c.2239+2418A>G		intron_variant	Intron 7 of 11			ENSP00000512809.1
CNNM1	ENST00000488090.1	n.344+2418A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0970 AC: 14758 AN: 152092 Hom.: 1020 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0972 AC: 14799 AN: 152210 Hom.: 1026 Cov.: 32 AF XY: 0.0958 AC XY: 7132 AN XY: 74430

African (AFR) AF: 0.185 AC: 7687 AN: 41490

American (AMR) AF: 0.0659 AC: 1008 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.0841 AC: 436 AN: 5186

South Asian (SAS) AF: 0.140 AC: 673 AN: 4818

European-Finnish (FIN) AF: 0.0440 AC: 467 AN: 10622

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.0594 AC: 4037 AN: 68016

Other (OTH) AF: 0.0847 AC: 179 AN: 2114

Alfa AF: 0.0809 Hom.: 740

Bravo AF: 0.100

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.9
DANN	Benign	0.35
PhyloP100		0.86
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: rs2002059; hg19: chr10-101130855;