rs11191518

Positions:

• chr10-103023096-C-G
• chr10-103023096-C-T

Variant summary

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

The NM_017649.5(CNNM2):​c.1622-26611C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,892 control chromosomes in the GnomAD database, including 12,875 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 0.41 (12875 hom., cov: 31)
• Consequence: CNNM2 NM_017649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNNM2	NM_017649.5	c.1622-26611C>G		intron_variant		ENST00000369878.9
CNNM2	NM_199076.3	c.1622-26611C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNNM2	ENST00000369878.9	c.1622-26611C>G		intron_variant		1	NM_017649.5	P4
CNNM2	ENST00000433628.2	c.1622-26611C>G		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61939 AN: 151772 Hom.: 12861 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.408 AC: 61995 AN: 151892 Hom.: 12875 Cov.: 31 AF XY: 0.407 AC XY: 30183 AN XY: 74220

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.422

Alfa AF: 0.284 Hom.: 738

Bravo AF: 0.409

Asia WGS AF: 0.470 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.18

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: rs11191518; hg19: chr10-104782853;