Genetic Variant CEMIP2:c.3956-6_3956-3delTTTT (chr9-71685395-TAAAA-T) – 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.3956-6_3956-3delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 1,062,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000044 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CEMIP2
NM_013390.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.98

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:

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ACMG classification

Classification was made for transcript

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

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	Effect	Exon Rank	Protein	UniProt
CEMIP2	NM_013390.3	MANE Select	c.3956-6_3956-3delTTTT	splice_region intron	N/A	NP_037522.1	Q9UHN6-1
CEMIP2	NM_001135820.2		c.3767-6_3767-3delTTTT	splice_region intron	N/A	NP_001129292.1	Q9UHN6-2
CEMIP2	NM_001349784.2		c.2042-6_2042-3delTTTT	splice_region intron	N/A	NP_001336713.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CEMIP2	ENST00000377044.9	TSL:1 MANE Select	c.3956-6_3956-3delTTTT	splice_region intron	N/A	ENSP00000366243.4	Q9UHN6-1
CEMIP2	ENST00000377066.9	TSL:1	c.3767-6_3767-3delTTTT	splice_region intron	N/A	ENSP00000366266.5	Q9UHN6-2
CEMIP2	ENST00000538669.1	TSL:1	n.1687-6_1687-3delTTTT	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

116356

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000442

AC:

AN:

1062340

Hom.:

AF XY:

0.0000433

AC XY:

AN XY:

507778

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

22246

American (AMR)

AF:

0.000260

AC:

AN:

11534

Ashkenazi Jewish (ASJ)

AF:

0.000133

AC:

AN:

15036

East Asian (EAS)

AF:

0.000115

AC:

AN:

26186

South Asian (SAS)

AF:

0.000224

AC:

AN:

31212

European-Finnish (FIN)

AF:

0.0000827

AC:

AN:

24170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2952

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

885780

Other (OTH)

AF:

0.0000925

AC:

AN:

43224

⚠️ 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: 0.243

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

116356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

54086

African (AFR)

AF:

0.00

AC:

AN:

29244

American (AMR)

AF:

0.00

AC:

AN:

10662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3084

East Asian (EAS)

AF:

0.00

AC:

AN:

4212

South Asian (SAS)

AF:

0.00

AC:

AN:

3512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59302

Other (OTH)

AF:

0.00

AC:

AN:

1534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.0

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.

9-71685395-TAAAAAAAAAAAAA-TAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over