11-123073585-C-T

Variant names:

• chr11-123073585-C-T
• rs142456942
• NM_024769.5:c.1011G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_024769.5(CLMP):​c.1011G>A​(p.Gly337Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0083 in 1,614,246 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (85 hom.)
• Consequence: CLMP NM_024769.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.796

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]

ENSG00000288061 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-123073585-C-T is Benign according to our data. Variant chr11-123073585-C-T is described in ClinVar as [Benign]. Clinvar id is 787547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.796 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00578 (880/152354) while in subpopulation SAS AF= 0.0217 (105/4830). AF 95% confidence interval is 0.0184. There are 3 homozygotes in gnomad4. There are 446 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLMP	NM_024769.5	c.1011G>A	p.Gly337Gly	synonymous_variant	Exon 7 of 7	ENST00000448775.4	NP_079045.1
LOC124902775	XR_007062927.1	n.871-9429C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLMP	ENST00000448775.4	c.1011G>A	p.Gly337Gly	synonymous_variant	Exon 7 of 7	1	NM_024769.5	ENSP00000405577.2
CLMP	ENST00000530371.5	n.485G>A		non_coding_transcript_exon_variant	Exon 4 of 4	4
ENSG00000288061	ENST00000660892.2	n.226+10072C>T		intron_variant	Intron 2 of 2
CLMP	ENST00000527977.5	n.*121G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00577 AC: 879 AN: 152234 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00786

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00703 AC: 1767 AN: 251486 Hom.: 19 AF XY: 0.00828 AC XY: 1126 AN XY: 135918

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0202

Gnomad FIN exome AF: 0.00273

Gnomad NFE exome AF: 0.00719

Gnomad OTH exome AF: 0.00798

GnomAD4 exome AF: 0.00856 AC: 12511 AN: 1461892 Hom.: 85 Cov.: 31 AF XY: 0.00884 AC XY: 6431 AN XY: 727248

Gnomad4 AFR exome AF: 0.00125

Gnomad4 AMR exome AF: 0.00230

Gnomad4 ASJ exome AF: 0.0145

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0200

Gnomad4 FIN exome AF: 0.00249

Gnomad4 NFE exome AF: 0.00863

Gnomad4 OTH exome AF: 0.00755

GnomAD4 genome AF: 0.00578 AC: 880 AN: 152354 Hom.: 3 Cov.: 32 AF XY: 0.00599 AC XY: 446 AN XY: 74492

Gnomad4 AFR AF: 0.00176

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00786

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00752 Hom.: 4

Bravo AF: 0.00484

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.00911

EpiControl AF: 0.00818

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142456942; hg19: chr11-122944293;