Genetic Variant CEMIP:c.94+78G>C (chr15-80874051-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.291

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

CEMIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CEMIP	NM_001293298.2	MANE Select	c.94+78G>C	intron	N/A	NP_001280227.1	Q8WUJ3-1
CEMIP	NM_001293304.2		c.94+78G>C	intron	N/A	NP_001280233.1	Q8WUJ3-1
CEMIP	NM_018689.3		c.94+78G>C	intron	N/A	NP_061159.1	Q8WUJ3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CEMIP	ENST00000394685.8	TSL:1 MANE Select	c.94+78G>C	intron	N/A	ENSP00000378177.3	Q8WUJ3-1
CEMIP	ENST00000220244.7	TSL:1	c.94+78G>C	intron	N/A	ENSP00000220244.3	Q8WUJ3-1
CEMIP	ENST00000356249.9	TSL:1	c.94+78G>C	intron	N/A	ENSP00000348583.5	Q8WUJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3521

AN:

152206

Hom.:

151

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0849

AC:

2385

AN:

28108

American (AMR)

AF:

0.00384

AC:

136

AN:

35462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24032

East Asian (EAS)

AF:

0.00

AC:

AN:

34922

South Asian (SAS)

AF:

0.000185

AC:

AN:

75732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43736

Middle Eastern (MID)

AF:

0.00169

AC:

AN:

5310

European-Non Finnish (NFE)

AF:

0.0000928

AC:

AN:

916310

Other (OTH)

AF:

0.00551

AC:

287

AN:

52128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

143

287

430

574

717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0232

AC:

3528

AN:

152324

Hom.:

151

Cov.:

AF XY:

0.0219

AC XY:

1634

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0807

AC:

3353

AN:

41562

American (AMR)

AF:

0.00791

AC:

121

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68040

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

160

319

479

638

798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.0270

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.91

(source)

DANN

Benign

0.62

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over