rs748696

Variant names:

• chr15-80801547-G-A
• rs748696
• NM_001293298.2:c.-176+21933G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-80801547-G-A
• chr15-80801547-G-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+21933G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,114 control chromosomes in the GnomAD database, including 10,775 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 0.36 (10775 hom., cov: 33)
• Consequence: CEMIP NM_001293298.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• 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

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 (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP	NM_001293298.2	c.-176+21933G>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+21933G>A		intron_variant	Intron 1 of 29	1	NM_001293298.2	ENSP00000378177.3
CEMIP	ENST00000220244.7	c.-17+21933G>A		intron_variant	Intron 1 of 28	1		ENSP00000220244.3
CEMIP	ENST00000356249.9	c.-116+21933G>A		intron_variant	Intron 1 of 29	1		ENSP00000348583.5

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54253 AN: 151996 Hom.: 10776 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.357 AC: 54249 AN: 152114 Hom.: 10775 Cov.: 33 AF XY: 0.354 AC XY: 26302 AN XY: 74364

African (AFR) AF: 0.213 AC: 8854 AN: 41510

American (AMR) AF: 0.295 AC: 4517 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3468

East Asian (EAS) AF: 0.154 AC: 796 AN: 5176

South Asian (SAS) AF: 0.196 AC: 946 AN: 4816

European-Finnish (FIN) AF: 0.523 AC: 5518 AN: 10558

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30970 AN: 67974

Other (OTH) AF: 0.340 AC: 719 AN: 2114

Alfa AF: 0.420 Hom.: 60840

Bravo AF: 0.337

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.9
DANN	Benign	0.47
PhyloP100		-0.093
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: rs748696; hg19: chr15-81093888;