rs11190062

Positions:

• chr10-99345245-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.1574-12267A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,208 control chromosomes in the GnomAD database, including 54,125 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 0.84 (54125 hom., cov: 32)
• Consequence: CNNM1 NM_020348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNNM1	NM_020348.3	c.1574-12267A>G		intron_variant		ENST00000356713.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM1	ENST00000356713.5	c.1574-12267A>G		intron_variant		1	NM_020348.3	P4
CNNM1	ENST00000696687.1	c.1574-12267A>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127921 AN: 152090 Hom.: 54072 Cov.: 32

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.832

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

GnomAD4 genome AF: 0.841 AC: 128034 AN: 152208 Hom.: 54125 Cov.: 32 AF XY: 0.841 AC XY: 62566 AN XY: 74414

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.832

Alfa AF: 0.826 Hom.: 9284

Bravo AF: 0.836

Asia WGS AF: 0.865 AC: 3010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.80

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: rs11190062; hg19: chr10-101105002;