Genetic Variant CEMIP2:c.3956-10_3956-3dupTTTTTTTT (chr9-71685395-T-TAAAAAAAA) – 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.3956-10_3956-3dupTTTTTTTT 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 0.00068 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

CEMIP2
NM_013390.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.302

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.3956-10_3956-3dupTTTTTTTT		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_3956-2insTTTTTTTT		splice_region_variant, intron_variant	Intron 23 of 23	1	NM_013390.3	ENSP00000366243.4		Q9UHN6-1

Frequencies

GnomAD3 genomes

AF:

0.000680

AC:

AN:

116094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000469

Gnomad ASJ

AF:

0.000325

Gnomad EAS

AF:

0.00167

Gnomad SAS

AF:

0.000285

Gnomad FIN

AF:

0.000532

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000388

Gnomad OTH

AF:

0.000652

GnomAD4 exome

AF:

0.000234

AC:

249

AN:

1062252

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

126

AN XY:

507716

show subpopulations

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

African (AFR)

AF:

0.000405

AC:

AN:

22240

American (AMR)

AF:

0.00139

AC:

AN:

11542

Ashkenazi Jewish (ASJ)

AF:

0.000332

AC:

AN:

15038

East Asian (EAS)

AF:

0.000650

AC:

AN:

26174

South Asian (SAS)

AF:

0.00218

AC:

AN:

31166

European-Finnish (FIN)

AF:

0.000331

AC:

AN:

24168

Middle Eastern (MID)

AF:

0.000678

AC:

AN:

2952

European-Non Finnish (NFE)

AF:

0.000124

AC:

110

AN:

885756

Other (OTH)

AF:

0.000324

AC:

AN:

43216

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.339

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000681

AC:

AN:

116070

Hom.:

Cov.:

AF XY:

0.000778

AC XY:

AN XY:

53970

show subpopulations

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

African (AFR)

AF:

0.00134

AC:

AN:

29122

American (AMR)

AF:

0.000469

AC:

AN:

10654

Ashkenazi Jewish (ASJ)

AF:

0.000325

AC:

AN:

3080

East Asian (EAS)

AF:

0.00168

AC:

AN:

4178

South Asian (SAS)

AF:

0.000287

AC:

AN:

3482

European-Finnish (FIN)

AF:

0.000532

AC:

AN:

3756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.000388

AC:

AN:

59230

Other (OTH)

AF:

0.000649

AC:

AN:

1540

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.301

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

LitVar

Below is the list of publications found by LitVar for variant 9:71685395 T>TAAAAAAAA . It may be empty.

chr9-71685395-T-TAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over