rs35092028

Positions:

• chr15-80929151-C-T

Variant summary

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

The NM_001293298.2(CEMIP):​c.2589C>T​(p.Ser863=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,614,100 control chromosomes in the GnomAD database, including 418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (52 hom., cov: 32)
  • Exomes 𝑓: 0.022 (366 hom.)
• Consequence: CEMIP NM_001293298.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.91

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-80929151-C-T is Benign according to our data. Variant chr15-80929151-C-T is described in ClinVar as [Benign]. Clinvar id is 585661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.91 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.024 (3647/152222) while in subpopulation AFR AF= 0.0281 (1169/41542). AF 95% confidence interval is 0.0268. There are 52 homozygotes in gnomad4. There are 1651 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEMIP	NM_001293298.2	c.2589C>T	p.Ser863=	synonymous_variant	21/30	ENST00000394685.8	NP_001280227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEMIP	ENST00000394685.8	c.2589C>T	p.Ser863=	synonymous_variant	21/30	1	NM_001293298.2	ENSP00000378177	P1
CEMIP	ENST00000220244.7	c.2589C>T	p.Ser863=	synonymous_variant	20/29	1		ENSP00000220244	P1
CEMIP	ENST00000356249.9	c.2589C>T	p.Ser863=	synonymous_variant	21/30	1		ENSP00000348583	P1

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3643 AN: 152104 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0258

Gnomad OTH AF: 0.0344

GnomAD3 exomes AF: 0.0195 AC: 4909 AN: 251488 Hom.: 78 AF XY: 0.0194 AC XY: 2643 AN XY: 135918

Gnomad AFR exome AF: 0.0314

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.0268

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.00385

Gnomad FIN exome AF: 0.0202

Gnomad NFE exome AF: 0.0257

Gnomad OTH exome AF: 0.0239

GnomAD4 exome AF: 0.0215 AC: 31451 AN: 1461878 Hom.: 366 Cov.: 32 AF XY: 0.0211 AC XY: 15371 AN XY: 727242

Gnomad4 AFR exome AF: 0.0285

Gnomad4 AMR exome AF: 0.0157

Gnomad4 ASJ exome AF: 0.0273

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00412

Gnomad4 FIN exome AF: 0.0187

Gnomad4 NFE exome AF: 0.0236

Gnomad4 OTH exome AF: 0.0210

GnomAD4 genome AF: 0.0240 AC: 3647 AN: 152222 Hom.: 52 Cov.: 32 AF XY: 0.0222 AC XY: 1651 AN XY: 74416

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.0258

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0239 Hom.: 36

Bravo AF: 0.0237

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.0288

EpiControl AF: 0.0277

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Feb 03, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

CEMIP-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs35092028; hg19: chr15-81221492;