Genetic Variant CEMIP:p.Lys1360del (chr15-80948905-TGAA-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBS1BS2

The NM_001293298.2(CEMIP):c.4078_4080delAAG(p.Lys1360del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.017 in 1,614,116 control chromosomes in the GnomAD database, including 306 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 9 hom., cov: 32)

Exomes 𝑓: 0.018 ( 297 hom. )

Consequence

CEMIP
NM_001293298.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.74

Variant links:

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 links:

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 links:

ENSG00000259546 (HGNC:):

ENSG00000259546 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001293298.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 15-80948905-TGAA-T is Benign according to our data. Variant chr15-80948905-TGAA-T is described in ClinVar as [Benign]. Clinvar id is 804686.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1722/152274) while in subpopulation NFE AF= 0.0195 (1327/68008). AF 95% confidence interval is 0.0186. There are 9 homozygotes in gnomad4. There are 765 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP	NM_001293298.2 link	c.4078_4080delAAG	p.Lys1360del	conservative_inframe_deletion	Exon 30 of 30	ENST00000394685.8	NP_001280227.1	Q8WUJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP	ENST00000394685.8 link	c.4078_4080delAAG	p.Lys1360del	conservative_inframe_deletion	Exon 30 of 30	1	NM_001293298.2	ENSP00000378177.3		Q8WUJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1723

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0195

Gnomad OTH

AF:

0.00910

GnomAD3 exomes

AF:

0.0106

AC:

2673

AN:

251480

Hom.:

AF XY:

0.0107

AC XY:

1453

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00332

Gnomad AMR exome

AF:

0.00642

Gnomad ASJ exome

AF:

0.00972

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00307

Gnomad FIN exome

AF:

0.00328

Gnomad NFE exome

AF:

0.0182

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0176

AC:

25784

AN:

1461842

Hom.:

297

AF XY:

0.0172

AC XY:

12517

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00269

Gnomad4 AMR exome

AF:

0.00684

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00316

Gnomad4 FIN exome

AF:

0.00341

Gnomad4 NFE exome

AF:

0.0213

Gnomad4 OTH exome

AF:

0.0151

GnomAD4 genome

AF:

0.0113

AC:

1722

AN:

152274

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

765

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.0195

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0198

EpiControl

AF:

0.0153

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 26, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over