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rs4724348

Variant summary

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

The NM_031443.4(CCM2):c.31-18613T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 151,774 control chromosomes in the GnomAD database, including 57,249 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 0.87 ( 57249 hom., cov: 29)

Consequence

CCM2
NM_031443.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308
Variant links:
Genes affected
CCM2 (HGNC:21708): (CCM2 scaffold protein) This gene encodes a scaffold protein that functions in the stress-activated p38 Mitogen-activated protein kinase (MAPK) signaling cascade. The protein interacts with SMAD specific E3 ubiquitin protein ligase 1 (also known as SMURF1) via a phosphotyrosine binding domain to promote RhoA degradation. The protein is required for normal cytoskeletal structure, cell-cell interactions, and lumen formation in endothelial cells. Mutations in this gene result in cerebral cavernous malformations. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

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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=-0.95).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCM2NM_031443.4 linkuse as main transcriptc.31-18613T>C intron_variant ENST00000258781.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCM2ENST00000258781.11 linkuse as main transcriptc.31-18613T>C intron_variant 1 NM_031443.4 P1Q9BSQ5-1

Frequencies

GnomAD3 genomes
AF:
0.866
AC:
131354
AN:
151656
Hom.:
57192
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.961
Gnomad AMI
AF:
0.900
Gnomad AMR
AF:
0.826
Gnomad ASJ
AF:
0.776
Gnomad EAS
AF:
0.910
Gnomad SAS
AF:
0.857
Gnomad FIN
AF:
0.877
Gnomad MID
AF:
0.771
Gnomad NFE
AF:
0.819
Gnomad OTH
AF:
0.823
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.866
AC:
131472
AN:
151774
Hom.:
57249
Cov.:
29
AF XY:
0.869
AC XY:
64426
AN XY:
74166
show subpopulations
Gnomad4 AFR
AF:
0.961
Gnomad4 AMR
AF:
0.826
Gnomad4 ASJ
AF:
0.776
Gnomad4 EAS
AF:
0.910
Gnomad4 SAS
AF:
0.857
Gnomad4 FIN
AF:
0.877
Gnomad4 NFE
AF:
0.819
Gnomad4 OTH
AF:
0.823
Alfa
AF:
0.840
Hom.:
6688
Bravo
AF:
0.871
Asia WGS
AF:
0.861
AC:
2996
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
Cadd
Benign
4.1
Dann
Benign
0.50

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: rs4724348; hg19: chr7-45059239; API