NM_001293298.2:c.-176+18128G>A

Variant names:

• chr15-80797742-G-A
• rs1872234
• NM_001293298.2:c.-176+18128G>A

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+18128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,176 control chromosomes in the GnomAD database, including 52,129 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 0.80 (52129 hom., cov: 32)
• Consequence: CEMIP NM_001293298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP	NM_001293298.2	c.-176+18128G>A		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+18128G>A		intron_variant	Intron 1 of 29	1	NM_001293298.2	ENSP00000378177.3
CEMIP	ENST00000220244.7	c.-17+18128G>A		intron_variant	Intron 1 of 28	1		ENSP00000220244.3
CEMIP	ENST00000356249.9	c.-116+18128G>A		intron_variant	Intron 1 of 29	1		ENSP00000348583.5

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121610 AN: 152058 Hom.: 52129 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.799 AC: 121646 AN: 152176 Hom.: 52129 Cov.: 32 AF XY: 0.806 AC XY: 59989 AN XY: 74398

African (AFR) AF: 0.457 AC: 18951 AN: 41460

American (AMR) AF: 0.887 AC: 13559 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 3167 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5182

South Asian (SAS) AF: 0.927 AC: 4471 AN: 4824

European-Finnish (FIN) AF: 0.961 AC: 10194 AN: 10604

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63260 AN: 68022

Other (OTH) AF: 0.828 AC: 1750 AN: 2114

Alfa AF: 0.886 Hom.: 67064

Bravo AF: 0.777

Asia WGS AF: 0.926 AC: 3218 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.54
PhyloP100		1.1
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: rs1872234; hg19: chr15-81090083;