rs11191548

Positions:

• chr10-103086421-T-C

Variant summary

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

The ENST00000369878.9(CNNM2):​c.*9241T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,024 control chromosomes in the GnomAD database, including 850 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 0.091 (850 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNNM2 ENST00000369878.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNNM2	NM_017649.5	c.*9241T>C		3_prime_UTR_variant	8/8	ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.*9241T>C		3_prime_UTR_variant	7/7		NP_951058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9	c.*9241T>C		3_prime_UTR_variant	8/8	1	NM_017649.5	ENSP00000358894	P4

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13764 AN: 151906 Hom.: 844 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0702

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.101

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0907 AC: 13785 AN: 152024 Hom.: 850 Cov.: 32 AF XY: 0.0926 AC XY: 6883 AN XY: 74320

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0702

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.0899

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0932 Hom.: 1174

Bravo AF: 0.0940

Asia WGS AF: 0.198 AC: 684 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.78

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: rs11191548; hg19: chr10-104846178;