rs11191499

Positions:

• chr10-103004514-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017649.5(CNNM2):​c.1622-45193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0948 in 152,276 control chromosomes in the GnomAD database, including 891 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 0.095 (891 hom., cov: 32)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775

Genes affected

CNNM2 (HGNC:103): (cyclin and CBS domain divalent metal cation transport mediator 2) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in magnesium homeostasis by mediating the epithelial transport and renal reabsorption of Mg2+. Mutations in this gene are associated with renal hypomagnesemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNNM2	NM_017649.5	c.1622-45193T>C		intron_variant		ENST00000369878.9
CNNM2	NM_199076.3	c.1622-45193T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM2	ENST00000369878.9	c.1622-45193T>C		intron_variant		1	NM_017649.5	P4
CNNM2	ENST00000433628.2	c.1622-45193T>C		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14421 AN: 152158 Hom.: 886 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0948 AC: 14441 AN: 152276 Hom.: 891 Cov.: 32 AF XY: 0.0968 AC XY: 7211 AN XY: 74462

Gnomad4 AFR AF: 0.0603

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.0757

Gnomad4 NFE AF: 0.0910

Gnomad4 OTH AF: 0.106

Alfa AF: 0.105 Hom.: 171

Bravo AF: 0.0983

Asia WGS AF: 0.200 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.6
DANN	Benign	0.57

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: rs11191499; hg19: chr10-104764271;