rs35541581

chr15-80879723-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001293298.2(CEMIP):c.249G>A(p.Leu83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,614,116 control chromosomes in the GnomAD database, including 1,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (1042 hom., cov: 33)
  • Exomes 𝑓: 0.0083 (924 hom.)
• Consequence: CEMIP NM_001293298.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.25

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=-0.94).
• BP6: Variant 15-80879723-G-A is Benign according to our data. Variant chr15-80879723-G-A is described in ClinVar as [Benign]. Clinvar id is 585660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEMIP	NM_001293298.2	c.249G>A	p.Leu83=	synonymous_variant	5/30	ENST00000394685.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEMIP	ENST00000394685.8	c.249G>A	p.Leu83=	synonymous_variant	5/30	1	NM_001293298.2	P1
CEMIP	ENST00000220244.7	c.249G>A	p.Leu83=	synonymous_variant	4/29	1		P1
CEMIP	ENST00000356249.9	c.249G>A	p.Leu83=	synonymous_variant	5/30	1		P1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9702 AN: 152136 Hom.: 1033 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00272

Gnomad OTH AF: 0.0469

GnomAD3 exomes AF: 0.0185 AC: 4644 AN: 251230 Hom.: 440 AF XY: 0.0138 AC XY: 1878 AN XY: 135780

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0150

Gnomad ASJ exome AF: 0.00774

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00263

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.00831 AC: 12155 AN: 1461862 Hom.: 924 Cov.: 31 AF XY: 0.00734 AC XY: 5336 AN XY: 727238

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.0168

Gnomad4 ASJ exome AF: 0.00754

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000533

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.00219

Gnomad4 OTH exome AF: 0.0177

GnomAD4 genome AF: 0.0640 AC: 9742 AN: 152254 Hom.: 1042 Cov.: 33 AF XY: 0.0623 AC XY: 4641 AN XY: 74454

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00272

Gnomad4 OTH AF: 0.0483

Alfa AF: 0.0305 Hom.: 220

Bravo AF: 0.0727

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00284

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 23, 2018	- -

CEMIP-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 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	-0.94
Cadd	Benign	0.038
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35541581; hg19: chr15-81172064; COSMIC: COSV104527602;