rs7952397

Variant names:

• chr11-123186433-G-A
• rs7952397
• NM_024769.5:c.28+8480C>T

Variant summary

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

The ENST00000448775.4(CLMP):​c.28+8480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,968 control chromosomes in the GnomAD database, including 8,873 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 0.22 (8873 hom., cov: 32)
• Consequence: CLMP ENST00000448775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• 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: 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448775.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLMP	NM_024769.5	MANE Select	c.28+8480C>T		intron	N/A	NP_079045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLMP	ENST00000448775.4	TSL:1 MANE Select	c.28+8480C>T		intron	N/A	ENSP00000405577.2
	CLMP	ENST00000715744.1		c.28+8480C>T		intron	N/A	ENSP00000520511.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33752 AN: 151852 Hom.: 8829 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.0857

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.223 AC: 33855 AN: 151968 Hom.: 8873 Cov.: 32 AF XY: 0.220 AC XY: 16377 AN XY: 74300

African (AFR) AF: 0.632 AC: 26150 AN: 41402

American (AMR) AF: 0.200 AC: 3059 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3470

East Asian (EAS) AF: 0.152 AC: 785 AN: 5150

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4816

European-Finnish (FIN) AF: 0.0654 AC: 691 AN: 10568

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0340 AC: 2309 AN: 67978

Other (OTH) AF: 0.177 AC: 371 AN: 2100

Alfa AF: 0.138 Hom.: 2862

Bravo AF: 0.258

Asia WGS AF: 0.136 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.55
PhyloP100		-2.3
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: rs7952397; hg19: chr11-123057141;