11-123073633-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_024769.5(CLMP):c.963C>T(p.Asp321=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
CLMP
NM_024769.5 synonymous
NM_024769.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.942
Genes affected
CLMP (HGNC:24039): (CXADR like membrane protein) This gene encodes a type I transmembrane protein that is localized to junctional complexes between endothelial and epithelial cells and may have a role in cell-cell adhesion. Expression of this gene in white adipose tissue is implicated in adipocyte maturation and development of obesity. This gene is also essential for normal intestinal development and mutations in the gene are associated with congenital short bowel syndrome. [provided by RefSeq, Aug 2015]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 11-123073633-G-A is Benign according to our data. Variant chr11-123073633-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3044307.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.942 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000328 (48/1461888) while in subpopulation AMR AF= 0.000201 (9/44724). AF 95% confidence interval is 0.000104. There are 0 homozygotes in gnomad4_exome. There are 20 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLMP | NM_024769.5 | c.963C>T | p.Asp321= | synonymous_variant | 7/7 | ENST00000448775.4 | |
LOC124902775 | XR_007062927.1 | n.871-9381G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLMP | ENST00000448775.4 | c.963C>T | p.Asp321= | synonymous_variant | 7/7 | 1 | NM_024769.5 | P1 | |
ENST00000660892.2 | n.226+10120G>A | intron_variant, non_coding_transcript_variant | |||||||
CLMP | ENST00000530371.5 | n.437C>T | non_coding_transcript_exon_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152226Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
9
AN:
152226
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251454Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135900
GnomAD3 exomes
AF:
AC:
13
AN:
251454
Hom.:
AF XY:
AC XY:
4
AN XY:
135900
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727244
GnomAD4 exome
AF:
AC:
48
AN:
1461888
Hom.:
Cov.:
31
AF XY:
AC XY:
20
AN XY:
727244
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74490
GnomAD4 genome
?
AF:
AC:
9
AN:
152344
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74490
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CLMP-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 05, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at