9-71685385-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_013390.3(CEMIP2):c.3964A>G(p.Ile1322Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000556 in 1,439,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000019 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

CEMIP2
NM_013390.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.196

Publications

0 publications found

Variant links:

Genes affected

CEMIP2 (HGNC:11869): (cell migration inducing hyaluronidase 2) This gene encodes a type II transmembrane protein that belongs to the interferon-induced transmembrane (IFITM) protein superfamily. The encoded protein functions as a cell surface hyaluronidase that cleaves extracellular high molecular weight hyaluronan into intermediate size fragments before internalization and degradation in the lysosome. It also has an interferon-mediated antiviral function in humans through activation of the JAK STAT signaling pathway. The activation of this gene by transcription factor SOX4 in breast cancer cells has been shown to mediate the pathological effects of SOX4 on cancer progression. Naturally occurring mutations in this gene are associated with autosomal recessive non-syndromic hearing loss. [provided by RefSeq, Mar 2017]

CEMIP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039858192).

BP6

Variant 9-71685385-T-C is Benign according to our data. Variant chr9-71685385-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3490219.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013390.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEMIP2	NM_013390.3	MANE Select	c.3964A>G	p.Ile1322Val	missense	Exon 24 of 24	NP_037522.1	Q9UHN6-1
CEMIP2	NM_001135820.2		c.3775A>G	p.Ile1259Val	missense	Exon 23 of 23	NP_001129292.1	Q9UHN6-2
CEMIP2	NM_001349784.2		c.2050A>G	p.Ile684Val	missense	Exon 24 of 24	NP_001336713.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEMIP2	ENST00000377044.9	TSL:1 MANE Select	c.3964A>G	p.Ile1322Val	missense	Exon 24 of 24	ENSP00000366243.4	Q9UHN6-1
CEMIP2	ENST00000377066.9	TSL:1	c.3775A>G	p.Ile1259Val	missense	Exon 23 of 23	ENSP00000366266.5	Q9UHN6-2
CEMIP2	ENST00000538669.1	TSL:1	n.1695A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000190

AC:

AN:

105302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000363

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

167486

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000450

AC:

AN:

1334460

Hom.:

Cov.:

AF XY:

0.00000457

AC XY:

AN XY:

656388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28486

American (AMR)

AF:

0.00

AC:

AN:

26646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21676

East Asian (EAS)

AF:

0.0000279

AC:

AN:

35798

South Asian (SAS)

AF:

0.00

AC:

AN:

66262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4948

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

1051934

Other (OTH)

AF:

0.00

AC:

AN:

54484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000190

AC:

AN:

105302

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

48908

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24962

American (AMR)

AF:

0.00

AC:

AN:

8370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2972

East Asian (EAS)

AF:

0.00

AC:

AN:

3850

South Asian (SAS)

AF:

0.00

AC:

AN:

3304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.0000363

AC:

AN:

55038

Other (OTH)

AF:

0.00

AC:

AN:

1376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.0

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.013

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.72

M_CAP

Benign

0.013

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.99

PhyloP100

0.20

PrimateAI

Benign

0.33

PROVEAN

Benign

0.50

REVEL

Benign

0.081

Sift

Benign

0.65

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.019

MutPred

0.26

Loss of sheet (P = 0.0817)

MVP

0.41

MPC

0.14

ClinPred

0.075

GERP RS

-0.99

Varity_R

0.014

gMVP

0.59

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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