15-80929151-C-T

Variant names:

• chr15-80929151-C-T
• rs35092028
• NM_001293298.2:c.2589C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001293298.2(CEMIP):​c.2589C>T​(p.Ser863Ser) 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
• Publications: 4 publications found

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]

CEMIP Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000259546 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001293298.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	NM_001293298.2	MANE Select	c.2589C>T	p.Ser863Ser	synonymous	Exon 21 of 30	NP_001280227.1	Q8WUJ3-1
	CEMIP	NM_001293304.2		c.2589C>T	p.Ser863Ser	synonymous	Exon 21 of 30	NP_001280233.1	Q8WUJ3-1
	CEMIP	NM_018689.3		c.2589C>T	p.Ser863Ser	synonymous	Exon 20 of 29	NP_061159.1	Q8WUJ3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	ENST00000394685.8	TSL:1 MANE Select	c.2589C>T	p.Ser863Ser	synonymous	Exon 21 of 30	ENSP00000378177.3	Q8WUJ3-1
	CEMIP	ENST00000220244.7	TSL:1	c.2589C>T	p.Ser863Ser	synonymous	Exon 20 of 29	ENSP00000220244.3	Q8WUJ3-1
	CEMIP	ENST00000356249.9	TSL:1	c.2589C>T	p.Ser863Ser	synonymous	Exon 21 of 30	ENSP00000348583.5	Q8WUJ3-1

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

GnomAD2 exomes AF: 0.0195 AC: 4909 AN: 251488 AF XY: 0.0194

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 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

African (AFR) AF: 0.0285 AC: 955 AN: 33480

American (AMR) AF: 0.0157 AC: 702 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0273 AC: 713 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00412 AC: 355 AN: 86258

European-Finnish (FIN) AF: 0.0187 AC: 998 AN: 53420

Middle Eastern (MID) AF: 0.0395 AC: 228 AN: 5768

European-Non Finnish (NFE) AF: 0.0236 AC: 26225 AN: 1111996

Other (OTH) AF: 0.0210 AC: 1271 AN: 60396

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

African (AFR) AF: 0.0281 AC: 1169 AN: 41542

American (AMR) AF: 0.0192 AC: 293 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4820

European-Finnish (FIN) AF: 0.0163 AC: 173 AN: 10612

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0258 AC: 1755 AN: 68014

Other (OTH) AF: 0.0341 AC: 72 AN: 2114

Alfa AF: 0.0247 Hom.: 41

Bravo AF: 0.0237

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.0288

EpiControl AF: 0.0277

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	CEMIP-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.83
PhyloP100		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs35092028; hg19: chr15-81221492;