11-123083783-C-T

Variant names:

• chr11-123083783-C-T
• rs112659755
• NM_024769.5:c.453G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_024769.5(CLMP):​c.453G>A​(p.Leu151Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,613,988 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (19 hom.)
• Consequence: CLMP NM_024769.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.879
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital short bowel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124902775 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 11-123083783-C-T is Benign according to our data. Variant chr11-123083783-C-T is described in ClinVar as Benign. ClinVar VariationId is 784224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.879 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0091 (1386/152290) while in subpopulation AFR AF = 0.0311 (1293/41570). AF 95% confidence interval is 0.0297. There are 14 homozygotes in GnomAd4. There are 663 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 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.453G>A	p.Leu151Leu	synonymous	Exon 4 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.453G>A	p.Leu151Leu	synonymous	Exon 4 of 7	ENSP00000405577.2	Q9H6B4
	CLMP	ENST00000950922.1		c.468G>A	p.Leu156Leu	synonymous	Exon 4 of 7	ENSP00000620981.1
	CLMP	ENST00000715744.1		c.453G>A	p.Leu151Leu	synonymous	Exon 4 of 7	ENSP00000520511.1	Q9H6B4

Frequencies

GnomAD3 genomes AF: 0.00909 AC: 1383 AN: 152172 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00274 AC: 689 AN: 251412 AF XY: 0.00202

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00101 AC: 1475 AN: 1461698 Hom.: 19 Cov.: 32 AF XY: 0.000877 AC XY: 638 AN XY: 727154

African (AFR) AF: 0.0314 AC: 1052 AN: 33468

American (AMR) AF: 0.00250 AC: 112 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00214 AC: 12 AN: 5620

European-Non Finnish (NFE) AF: 0.000144 AC: 160 AN: 1112008

Other (OTH) AF: 0.00210 AC: 127 AN: 60382

GnomAD4 genome AF: 0.00910 AC: 1386 AN: 152290 Hom.: 14 Cov.: 32 AF XY: 0.00890 AC XY: 663 AN XY: 74470

African (AFR) AF: 0.0311 AC: 1293 AN: 41570

American (AMR) AF: 0.00360 AC: 55 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68036

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00443 Hom.: 7

Bravo AF: 0.0104

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CLMP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		0.88
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs112659755; hg19: chr11-122954491;