NM_001293298.2:c.-175-22805G>T

Variant names:

• chr15-80850733-G-T
• rs906428
• NM_001293298.2:c.-175-22805G>T

Variant summary

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

The NM_001293298.2(CEMIP):​c.-175-22805G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,194 control chromosomes in the GnomAD database, including 1,556 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 0.13 (1556 hom., cov: 32)
• Consequence: CEMIP NM_001293298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	NM_001293298.2	MANE Select	c.-175-22805G>T		intron	N/A	NP_001280227.1
	CEMIP	NM_001293304.2		c.-115-22805G>T		intron	N/A	NP_001280233.1
	CEMIP	NM_018689.3		c.-16-23131G>T		intron	N/A	NP_061159.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	ENST00000394685.8	TSL:1 MANE Select	c.-175-22805G>T		intron	N/A	ENSP00000378177.3
	CEMIP	ENST00000220244.7	TSL:1	c.-16-23131G>T		intron	N/A	ENSP00000220244.3
	CEMIP	ENST00000356249.9	TSL:1	c.-115-22805G>T		intron	N/A	ENSP00000348583.5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19259 AN: 152076 Hom.: 1554 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.127 AC: 19265 AN: 152194 Hom.: 1556 Cov.: 32 AF XY: 0.125 AC XY: 9309 AN XY: 74412

African (AFR) AF: 0.0326 AC: 1353 AN: 41550

American (AMR) AF: 0.204 AC: 3119 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 295 AN: 3472

East Asian (EAS) AF: 0.132 AC: 681 AN: 5174

South Asian (SAS) AF: 0.189 AC: 914 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1199 AN: 10590

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11263 AN: 67984

Other (OTH) AF: 0.113 AC: 238 AN: 2112

Alfa AF: 0.156 Hom.: 3376

Bravo AF: 0.129

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.65
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs906428; hg19: chr15-81143074;