rs7914558

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017649.5(CNNM2):​c.1622-33556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,480 control chromosomes in the GnomAD database, including 12,724 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 ( 12724 hom., cov: 29)

Consequence

CNNM2
NM_017649.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.309
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNNM2NM_017649.5 linkc.1622-33556G>A intron_variant Intron 1 of 7 ENST00000369878.9 NP_060119.3 Q9H8M5-1
CNNM2NM_199076.3 linkc.1622-33556G>A intron_variant Intron 1 of 6 NP_951058.1 Q9H8M5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNNM2ENST00000369878.9 linkc.1622-33556G>A intron_variant Intron 1 of 7 1 NM_017649.5 ENSP00000358894.3 Q9H8M5-1
CNNM2ENST00000433628.2 linkc.1622-33556G>A intron_variant Intron 1 of 6 2 ENSP00000392875.2 Q9H8M5-2

Frequencies

GnomAD3 genomes
AF:
0.406
AC:
61477
AN:
151362
Hom.:
12712
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.373
Gnomad AMI
AF:
0.351
Gnomad AMR
AF:
0.400
Gnomad ASJ
AF:
0.437
Gnomad EAS
AF:
0.560
Gnomad SAS
AF:
0.450
Gnomad FIN
AF:
0.367
Gnomad MID
AF:
0.427
Gnomad NFE
AF:
0.418
Gnomad OTH
AF:
0.416
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.406
AC:
61531
AN:
151480
Hom.:
12724
Cov.:
29
AF XY:
0.404
AC XY:
29924
AN XY:
73982
show subpopulations
Gnomad4 AFR
AF:
0.373
Gnomad4 AMR
AF:
0.400
Gnomad4 ASJ
AF:
0.437
Gnomad4 EAS
AF:
0.559
Gnomad4 SAS
AF:
0.450
Gnomad4 FIN
AF:
0.367
Gnomad4 NFE
AF:
0.418
Gnomad4 OTH
AF:
0.420
Alfa
AF:
0.419
Hom.:
16158
Bravo
AF:
0.407
Asia WGS
AF:
0.470
AC:
1631
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
1.1
DANN
Benign
0.40

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7914558; hg19: chr10-104775908; API