15-80793142-T-C

Variant names:

• chr15-80793142-T-C
• rs925111
• NM_001293298.2:c.-176+13528T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001293298.2(CEMIP):​c.-176+13528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,026 control chromosomes in the GnomAD database, including 28,264 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (28264 hom., cov: 31)
• Consequence: CEMIP NM_001293298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 5 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP	NM_001293298.2	c.-176+13528T>C		intron_variant	Intron 1 of 29	ENST00000394685.8	NP_001280227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP	ENST00000394685.8	c.-176+13528T>C		intron_variant	Intron 1 of 29	1	NM_001293298.2	ENSP00000378177.3
CEMIP	ENST00000220244.7	c.-17+13528T>C		intron_variant	Intron 1 of 28	1		ENSP00000220244.3
CEMIP	ENST00000356249.9	c.-116+13528T>C		intron_variant	Intron 1 of 29	1		ENSP00000348583.5

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88039 AN: 151908 Hom.: 28275 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.609

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.579 AC: 88033 AN: 152026 Hom.: 28264 Cov.: 31 AF XY: 0.578 AC XY: 42900 AN XY: 74278

African (AFR) AF: 0.281 AC: 11638 AN: 41460

American (AMR) AF: 0.570 AC: 8715 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2394 AN: 3466

East Asian (EAS) AF: 0.777 AC: 4021 AN: 5172

South Asian (SAS) AF: 0.650 AC: 3132 AN: 4818

European-Finnish (FIN) AF: 0.639 AC: 6752 AN: 10564

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49163 AN: 67948

Other (OTH) AF: 0.605 AC: 1280 AN: 2114

Alfa AF: 0.679 Hom.: 156425

Bravo AF: 0.561

Asia WGS AF: 0.639 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		-0.097
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: rs925111; hg19: chr15-81085483;