chr11-123073708-G-A

Variant names:

• chr11-123073708-G-A
• rs142239120
• NM_024769.5:c.888C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.95
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• congenital short bowel syndrome, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• congenital short bowel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288061 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 38 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024769.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLMP	NM_024769.5	MANE Select	c.888C>T	p.Ser296Ser	synonymous	Exon 7 of 7	NP_079045.1	Q9H6B4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLMP	ENST00000448775.4	TSL:1 MANE Select	c.888C>T	p.Ser296Ser	synonymous	Exon 7 of 7	ENSP00000405577.2	Q9H6B4
	CLMP	ENST00000950922.1		c.903C>T	p.Ser301Ser	synonymous	Exon 7 of 7	ENSP00000620981.1
	CLMP	ENST00000715744.1		c.888C>T	p.Ser296Ser	synonymous	Exon 7 of 7	ENSP00000520511.1	Q9H6B4

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 576 AN: 152250 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.00403 AC: 1012 AN: 250858 AF XY: 0.00415

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 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.: 38 Cov.: 31 AF XY: 0.00567 AC XY: 4124 AN XY: 727134

African (AFR) AF: 0.00102 AC: 34 AN: 33474

American (AMR) AF: 0.00349 AC: 156 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00249 AC: 65 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86246

European-Finnish (FIN) AF: 0.00165 AC: 88 AN: 53414

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 0.00708 AC: 7872 AN: 1111902

Other (OTH) AF: 0.00497 AC: 300 AN: 60384

GnomAD4 genome AF: 0.00379 AC: 577 AN: 152368 Hom.: 1 Cov.: 32 AF XY: 0.00364 AC XY: 271 AN XY: 74514

African (AFR) AF: 0.00101 AC: 42 AN: 41586

American (AMR) AF: 0.00392 AC: 60 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00616 AC: 419 AN: 68036

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00545 Hom.: 3

Bravo AF: 0.00398

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00578

EpiControl AF: 0.00682

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		3.0
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs142239120; hg19: chr11-122944416;