15-80947286-C-T

Variant names:

• chr15-80947286-C-T
• rs76575417
• NM_001293298.2:c.3958+221C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001293298.2(CEMIP):​c.3958+221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 522,208 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (25 hom.)
• Consequence: CEMIP NM_001293298.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.536
• Publications: 0 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]

MESD (HGNC:13520): (mesoderm development LRP chaperone) Predicted to enable low-density lipoprotein particle receptor binding activity. Involved in ossification and protein folding. Located in endoplasmic reticulum. Implicated in osteogenesis imperfecta type 20. [provided by Alliance of Genome Resources, Apr 2022]

MESD Gene-Disease associations (from GenCC):

• osteogenesis imperfecta, type 20

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• osteogenesis imperfecta type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259546 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-80947286-C-T is Benign according to our data. Variant chr15-80947286-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	NM_001293298.2	MANE Select	c.3958+221C>T		intron	N/A	NP_001280227.1	Q8WUJ3-1
	CEMIP	NM_001293304.2		c.3958+221C>T		intron	N/A	NP_001280233.1	Q8WUJ3-1
	CEMIP	NM_018689.3		c.3958+221C>T		intron	N/A	NP_061159.1	Q8WUJ3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP	ENST00000394685.8	TSL:1 MANE Select	c.3958+221C>T		intron	N/A	ENSP00000378177.3	Q8WUJ3-1
	CEMIP	ENST00000220244.7	TSL:1	c.3958+221C>T		intron	N/A	ENSP00000220244.3	Q8WUJ3-1
	CEMIP	ENST00000356249.9	TSL:1	c.3958+221C>T		intron	N/A	ENSP00000348583.5	Q8WUJ3-1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2854 AN: 152174 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00267 AC: 987 AN: 369916 Hom.: 25 Cov.: 0 AF XY: 0.00237 AC XY: 456 AN XY: 192526

African (AFR) AF: 0.0629 AC: 701 AN: 11142

American (AMR) AF: 0.00518 AC: 83 AN: 16028

Ashkenazi Jewish (ASJ) AF: 0.000171 AC: 2 AN: 11696

East Asian (EAS) AF: 0.00 AC: 0 AN: 26958

South Asian (SAS) AF: 0.000260 AC: 9 AN: 34566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25640

Middle Eastern (MID) AF: 0.00322 AC: 6 AN: 1866

European-Non Finnish (NFE) AF: 0.000331 AC: 73 AN: 220408

Other (OTH) AF: 0.00523 AC: 113 AN: 21612

GnomAD4 genome AF: 0.0188 AC: 2870 AN: 152292 Hom.: 100 Cov.: 32 AF XY: 0.0190 AC XY: 1411 AN XY: 74452

African (AFR) AF: 0.0657 AC: 2728 AN: 41552

American (AMR) AF: 0.00529 AC: 81 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68024

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.0195 Hom.: 5

Bravo AF: 0.0212

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.76
DANN	Benign	0.26
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism

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: rs76575417; hg19: chr15-81239627;