Genetic Variant CEMIP2:c.3956-9_3956-3dupTTTTTTT (chr9-71685395-T-TAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_013390.3(CEMIP2):c.3956-9_3956-3dupTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

CEMIP2
NM_013390.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.302

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP2	NM_013390.3 link	c.3956-9_3956-3dupTTTTTTT		splice_region_variant, intron_variant	Intron 23 of 23	ENST00000377044.9	NP_037522.1	Q9UHN6-1A0A024R229

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP2	ENST00000377044.9 link	c.3956-3_3956-2insTTTTTTT		splice_region_variant, intron_variant	Intron 23 of 23	1	NM_013390.3	ENSP00000366243.4		Q9UHN6-1

Frequencies

GnomAD3 genomes

AF:

0.000655

AC:

AN:

115946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000480

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000376

Gnomad ASJ

AF:

0.00131

Gnomad EAS

AF:

0.00143

Gnomad SAS

AF:

0.000285

Gnomad FIN

AF:

0.000533

Gnomad MID

AF:

0.00439

Gnomad NFE

AF:

0.000728

Gnomad OTH

AF:

0.000654

GnomAD2 exomes

AF:

0.00564

AC:

100

AN:

17724

AF XY:

0.00584

show subpopulations

Gnomad AFR exome

AF:

0.00644

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.0140

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00499

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.000321

AC:

341

AN:

1062164

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

180

AN XY:

507688

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000360

AC:

AN:

22234

American (AMR)

AF:

0.00122

AC:

AN:

11522

Ashkenazi Jewish (ASJ)

AF:

0.000798

AC:

AN:

15034

East Asian (EAS)

AF:

0.000994

AC:

AN:

26160

South Asian (SAS)

AF:

0.00218

AC:

AN:

31174

European-Finnish (FIN)

AF:

0.000373

AC:

AN:

24158

Middle Eastern (MID)

AF:

0.000677

AC:

AN:

2954

European-Non Finnish (NFE)

AF:

0.000213

AC:

189

AN:

885708

Other (OTH)

AF:

0.000301

AC:

AN:

43220

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.344

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000656

AC:

AN:

115924

Hom.:

Cov.:

AF XY:

0.000650

AC XY:

AN XY:

53886

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000479

AC:

AN:

29210

American (AMR)

AF:

0.000376

AC:

AN:

10634

Ashkenazi Jewish (ASJ)

AF:

0.00131

AC:

AN:

3064

East Asian (EAS)

AF:

0.00143

AC:

AN:

4186

South Asian (SAS)

AF:

0.000287

AC:

AN:

3480

European-Finnish (FIN)

AF:

0.000533

AC:

AN:

3754

Middle Eastern (MID)

AF:

0.00481

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.000728

AC:

AN:

59036

Other (OTH)

AF:

0.000652

AC:

AN:

1534

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.286

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.30

Splicing

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

Publications

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9-71685395-TAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over