15-80874051-G-C

Position:

• chr15-80874051-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001293298.2(CEMIP):​c.94+78G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,368,064 control chromosomes in the GnomAD database, including 266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (151 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (115 hom.)
• Consequence: CEMIP NM_001293298.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.291

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-80874051-G-C is Benign according to our data. Variant chr15-80874051-G-C is described in ClinVar as [Benign]. Clinvar id is 1236945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEMIP	NM_001293298.2	c.94+78G>C		intron_variant		ENST00000394685.8	NP_001280227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEMIP	ENST00000394685.8	c.94+78G>C		intron_variant		1	NM_001293298.2	ENSP00000378177.3
CEMIP	ENST00000220244.7	c.94+78G>C		intron_variant		1		ENSP00000220244.3
CEMIP	ENST00000356249.9	c.94+78G>C		intron_variant		1		ENSP00000348583.5

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3521 AN: 152206 Hom.: 151 Cov.: 33

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00240 AC: 2916 AN: 1215740 Hom.: 115 AF XY: 0.00207 AC XY: 1258 AN XY: 607666

Gnomad4 AFR exome AF: 0.0849

Gnomad4 AMR exome AF: 0.00384

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000928

Gnomad4 OTH exome AF: 0.00551

GnomAD4 genome AF: 0.0232 AC: 3528 AN: 152324 Hom.: 151 Cov.: 33 AF XY: 0.0219 AC XY: 1634 AN XY: 74486

Gnomad4 AFR AF: 0.0807

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00115 Hom.: 1

Bravo AF: 0.0270

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.91
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs28394231; hg19: chr15-81166392;