rs12574703

Variant names:

• chr11-123152924-G-A
• rs12574703
• NM_024769.5:c.28+41989C>T

Variant summary

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

The NM_024769.5(CLMP):​c.28+41989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 152,196 control chromosomes in the GnomAD database, including 371 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 0.055 (371 hom., cov: 32)
• Consequence: CLMP NM_024769.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLMP	NM_024769.5	c.28+41989C>T		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.28+41989C>T		intron_variant	Intron 1 of 6	1	NM_024769.5	ENSP00000405577.2
CLMP	ENST00000715744.1	c.28+41989C>T		intron_variant	Intron 1 of 6			ENSP00000520511.1

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8368 AN: 152078 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0712

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.0908

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0551

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

GnomAD4 genome AF: 0.0550 AC: 8371 AN: 152196 Hom.: 371 Cov.: 32 AF XY: 0.0576 AC XY: 4288 AN XY: 74412

African (AFR) AF: 0.0353 AC: 1467 AN: 41514

American (AMR) AF: 0.0710 AC: 1086 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1260 AN: 5172

South Asian (SAS) AF: 0.0910 AC: 439 AN: 4822

European-Finnish (FIN) AF: 0.0212 AC: 225 AN: 10606

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0509 AC: 3465 AN: 68008

Other (OTH) AF: 0.0565 AC: 119 AN: 2108

Alfa AF: 0.0534 Hom.: 471

Bravo AF: 0.0582

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.37
PhyloP100		3.3
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: rs12574703; hg19: chr11-123023632;