11-123115764-T-C

Variant names:

• chr11-123115764-T-C
• rs11607994
• NM_024769.5:c.29-17812A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024769.5(CLMP):​c.29-17812A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,088 control chromosomes in the GnomAD database, including 4,148 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 0.23 (4148 hom., cov: 31)
• Consequence: CLMP NM_024769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 2 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• congenital short bowel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288061 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLMP	NM_024769.5	c.29-17812A>G		intron_variant	Intron 1 of 6	ENST00000448775.4	NP_079045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLMP	ENST00000448775.4	c.29-17812A>G		intron_variant	Intron 1 of 6	1	NM_024769.5	ENSP00000405577.2
CLMP	ENST00000715744.1	c.29-17812A>G		intron_variant	Intron 1 of 6			ENSP00000520511.1
ENSG00000288061	ENST00000836643.1	n.226-20331T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34768 AN: 151968 Hom.: 4149 Cov.: 31

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.229 AC: 34783 AN: 152088 Hom.: 4148 Cov.: 31 AF XY: 0.229 AC XY: 16989 AN XY: 74340

African (AFR) AF: 0.269 AC: 11167 AN: 41472

American (AMR) AF: 0.288 AC: 4394 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3460

East Asian (EAS) AF: 0.219 AC: 1130 AN: 5170

South Asian (SAS) AF: 0.173 AC: 833 AN: 4822

European-Finnish (FIN) AF: 0.180 AC: 1903 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14015 AN: 68004

Other (OTH) AF: 0.218 AC: 459 AN: 2108

Alfa AF: 0.189 Hom.: 1518

Bravo AF: 0.242

Asia WGS AF: 0.216 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.5
DANN	Benign	0.50
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11607994; hg19: chr11-122986472;