Genetic Variant NM_024769.5:c.888C>T (chr11-123073708-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024769.5(CLMP):c.888C>T(p.Ser296Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,614,078 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 38 hom. )

Consequence

CLMP
NM_024769.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.95

Variant links:

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]

CLMP links:

ENSG00000288061 (HGNC:):

ENSG00000288061 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 11-123073708-G-A is Benign according to our data. Variant chr11-123073708-G-A is described in ClinVar as [Benign]. Clinvar id is 791496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.95 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00379 (577/152368) while in subpopulation NFE AF= 0.00616 (419/68036). AF 95% confidence interval is 0.00567. There are 1 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLMP	NM_024769.5 link	c.888C>T	p.Ser296Ser	synonymous_variant	Exon 7 of 7	ENST00000448775.4	NP_079045.1	Q9H6B4B4E3S3
LOC124902775	XR_007062927.1 link	n.871-9306G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLMP	ENST00000448775.4 link	c.888C>T	p.Ser296Ser	synonymous_variant	Exon 7 of 7	1	NM_024769.5	ENSP00000405577.2	Q9H6B4
CLMP	ENST00000527977.5 link	n.710C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	3
CLMP	ENST00000530371.5 link	n.362C>T		non_coding_transcript_exon_variant	Exon 4 of 4	4
ENSG00000288061	ENST00000660892.2 link	n.226+10195G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

576

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00393

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00614

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00403

AC:

1012

AN:

250858

Hom.:

AF XY:

0.00415

AC XY:

563

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.00689

Gnomad OTH exome

AF:

0.00589

GnomAD4 exome

AF:

0.00583

AC:

8525

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00567

AC XY:

4124

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00349

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00165

Gnomad4 NFE exome

AF:

0.00708

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00379

AC:

577

AN:

152368

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

271

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.00616

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00557

Hom.:

Bravo

AF:

0.00398

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00682

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over