chr10-99379424-G-A

Variant names:

• chr10-99379424-G-A
• rs6584273
• NM_020348.3:c.2340+2206G>A

Variant summary

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

The NM_020348.3(CNNM1):​c.2340+2206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,140 control chromosomes in the GnomAD database, including 1,148 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 0.090 (1148 hom., cov: 32)
• Consequence: CNNM1 NM_020348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020348.3. 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
	CNNM1	NM_020348.3	MANE Select	c.2340+2206G>A		intron	N/A	NP_065081.2
	CNNM1	NM_001345887.2		c.2403+2206G>A		intron	N/A	NP_001332816.1
	CNNM1	NM_001345889.2		c.2403+2206G>A		intron	N/A	NP_001332818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNNM1	ENST00000356713.5	TSL:1 MANE Select	c.2340+2206G>A		intron	N/A	ENSP00000349147.4
	CNNM1	ENST00000696687.1		c.2403+2206G>A		intron	N/A	ENSP00000512809.1

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13720 AN: 152022 Hom.: 1148 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0903 AC: 13740 AN: 152140 Hom.: 1148 Cov.: 32 AF XY: 0.0881 AC XY: 6556 AN XY: 74394

African (AFR) AF: 0.224 AC: 9290 AN: 41488

American (AMR) AF: 0.0520 AC: 796 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3472

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5164

South Asian (SAS) AF: 0.0657 AC: 316 AN: 4812

European-Finnish (FIN) AF: 0.0186 AC: 197 AN: 10600

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0402 AC: 2735 AN: 67994

Other (OTH) AF: 0.0668 AC: 141 AN: 2112

Alfa AF: 0.0824 Hom.: 723

Bravo AF: 0.0969

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.58
PhyloP100		0.29
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: rs6584273; hg19: chr10-101139181;