15-80947371-A-G

Variant names:

• chr15-80947371-A-G
• rs10519305
• ENST00000561312:c.*2154T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000561312(MESD):​c.*2154T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 380,846 control chromosomes in the GnomAD database, including 600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (210 hom., cov: 33)
  • Exomes 𝑓: 0.049 (390 hom.)
• Consequence: MESD ENST00000561312 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.48

Genes affected

MESD (HGNC:13520): (mesoderm development LRP chaperone) Predicted to enable low-density lipoprotein particle receptor binding activity. Involved in ossification and protein folding. Located in endoplasmic reticulum. Implicated in osteogenesis imperfecta type 20. [provided by Alliance of Genome Resources, Apr 2022]

CEMIP (HGNC:29213): (cell migration inducing hyaluronidase 1) Enables several functions, including clathrin heavy chain binding activity; hyaluronic acid binding activity; and hyalurononglucosaminidase activity. Involved in several processes, including hyaluronan catabolic process; positive regulation of protein phosphorylation; and positive regulation of transport. Located in clathrin-coated endocytic vesicle; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259546 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-80947371-A-G is Benign according to our data. Variant chr15-80947371-A-G is described in ClinVar as [Benign]. Clinvar id is 1248114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP	NM_001293298.2	c.3958+306A>G		intron_variant	Intron 29 of 29	ENST00000394685.8	NP_001280227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP	ENST00000394685.8	c.3958+306A>G		intron_variant	Intron 29 of 29	1	NM_001293298.2	ENSP00000378177.3

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6554 AN: 152224 Hom.: 210 Cov.: 33

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.0851

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0534

Gnomad OTH AF: 0.0364

GnomAD4 exome AF: 0.0493 AC: 11276 AN: 228504 Hom.: 390 Cov.: 0 AF XY: 0.0486 AC XY: 5897 AN XY: 121324

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.000488

Gnomad4 SAS exome AF: 0.0431

Gnomad4 FIN exome AF: 0.0871

Gnomad4 NFE exome AF: 0.0518

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0431 AC: 6559 AN: 152342 Hom.: 210 Cov.: 33 AF XY: 0.0455 AC XY: 3391 AN XY: 74508

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0747

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.0851

Gnomad4 NFE AF: 0.0533

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0471 Hom.: 38

Bravo AF: 0.0414

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs10519305; hg19: chr15-81239712;