rs2002059

chr10-99371098-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CNNM1	NM_020348.3	c.2177-5957A>G		intron_variant		ENST00000356713.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM1	ENST00000356713.5	c.2177-5957A>G		intron_variant		1	NM_020348.3	P4
CNNM1	ENST00000696687.1	c.2239+2418A>G		intron_variant				A2
CNNM1	ENST00000488090.1	n.344+2418A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.0841

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0440

Gnomad4 NFE AF: 0.0594

Gnomad4 OTH AF: 0.0847

Alfa AF: 0.0697 Hom.: 286

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

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: rs2002059; hg19: chr10-101130855;