NM_001293298.2:c.-176+3843T>A

Variant names:

• chr15-80783457-T-A
• rs16972342
• NM_001293298.2:c.-176+3843T>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+3843T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 152,276 control chromosomes in the GnomAD database, including 652 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 0.058 (652 hom., cov: 33)
• Consequence: CEMIP NM_001293298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 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.-176+3843T>A		intron	N/A	NP_001280227.1
	CEMIP	NM_001293304.2		c.-116+3843T>A		intron	N/A	NP_001280233.1
	CEMIP	NM_018689.3		c.-17+3843T>A		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.-176+3843T>A		intron	N/A	ENSP00000378177.3
	CEMIP	ENST00000220244.7	TSL:1	c.-17+3843T>A		intron	N/A	ENSP00000220244.3
	CEMIP	ENST00000356249.9	TSL:1	c.-116+3843T>A		intron	N/A	ENSP00000348583.5

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8890 AN: 152158 Hom.: 653 Cov.: 33

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0769

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0583 AC: 8882 AN: 152276 Hom.: 652 Cov.: 33 AF XY: 0.0624 AC XY: 4647 AN XY: 74448

African (AFR) AF: 0.0125 AC: 519 AN: 41574

American (AMR) AF: 0.0767 AC: 1172 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3472

East Asian (EAS) AF: 0.418 AC: 2152 AN: 5154

South Asian (SAS) AF: 0.138 AC: 665 AN: 4822

European-Finnish (FIN) AF: 0.0405 AC: 430 AN: 10622

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0510 AC: 3467 AN: 68026

Other (OTH) AF: 0.0591 AC: 125 AN: 2114

Alfa AF: 0.0467 Hom.: 39

Bravo AF: 0.0596

Asia WGS AF: 0.286 AC: 993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.4
DANN	Benign	0.72
PhyloP100		0.64
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: rs16972342; hg19: chr15-81075798;