9-71745180-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013390.3(CEMIP2):​c.872G>A​(p.Arg291His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,786 control chromosomes in the GnomAD database, including 44,492 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R291L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.26 ( 5343 hom., cov: 31)
Exomes 𝑓: 0.23 ( 39149 hom. )

Consequence

CEMIP2
NM_013390.3 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0037347674).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CEMIP2NM_013390.3 linkuse as main transcriptc.872G>A p.Arg291His missense_variant 4/24 ENST00000377044.9 NP_037522.1 Q9UHN6-1A0A024R229

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CEMIP2ENST00000377044.9 linkuse as main transcriptc.872G>A p.Arg291His missense_variant 4/241 NM_013390.3 ENSP00000366243.4 Q9UHN6-1
CEMIP2ENST00000377066.9 linkuse as main transcriptc.872G>A p.Arg291His missense_variant 4/231 ENSP00000366266.5 Q9UHN6-2
CEMIP2ENST00000542935.5 linkuse as main transcriptn.872G>A non_coding_transcript_exon_variant 4/241 ENSP00000437750.1 F5H6B2

Frequencies

GnomAD3 genomes
AF:
0.256
AC:
38804
AN:
151814
Hom.:
5328
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.333
Gnomad AMI
AF:
0.153
Gnomad AMR
AF:
0.241
Gnomad ASJ
AF:
0.165
Gnomad EAS
AF:
0.176
Gnomad SAS
AF:
0.351
Gnomad FIN
AF:
0.291
Gnomad MID
AF:
0.203
Gnomad NFE
AF:
0.212
Gnomad OTH
AF:
0.236
GnomAD3 exomes
AF:
0.240
AC:
60214
AN:
251268
Hom.:
7710
AF XY:
0.242
AC XY:
32862
AN XY:
135796
show subpopulations
Gnomad AFR exome
AF:
0.334
Gnomad AMR exome
AF:
0.240
Gnomad ASJ exome
AF:
0.172
Gnomad EAS exome
AF:
0.166
Gnomad SAS exome
AF:
0.343
Gnomad FIN exome
AF:
0.279
Gnomad NFE exome
AF:
0.210
Gnomad OTH exome
AF:
0.208
GnomAD4 exome
AF:
0.227
AC:
332274
AN:
1461854
Hom.:
39149
Cov.:
34
AF XY:
0.230
AC XY:
167230
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.332
Gnomad4 AMR exome
AF:
0.238
Gnomad4 ASJ exome
AF:
0.170
Gnomad4 EAS exome
AF:
0.181
Gnomad4 SAS exome
AF:
0.341
Gnomad4 FIN exome
AF:
0.275
Gnomad4 NFE exome
AF:
0.216
Gnomad4 OTH exome
AF:
0.226
GnomAD4 genome
AF:
0.256
AC:
38860
AN:
151932
Hom.:
5343
Cov.:
31
AF XY:
0.261
AC XY:
19381
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.334
Gnomad4 AMR
AF:
0.242
Gnomad4 ASJ
AF:
0.165
Gnomad4 EAS
AF:
0.176
Gnomad4 SAS
AF:
0.351
Gnomad4 FIN
AF:
0.291
Gnomad4 NFE
AF:
0.212
Gnomad4 OTH
AF:
0.237
Alfa
AF:
0.213
Hom.:
6766
Bravo
AF:
0.251
TwinsUK
AF:
0.221
AC:
821
ALSPAC
AF:
0.219
AC:
845
ESP6500AA
AF:
0.328
AC:
1447
ESP6500EA
AF:
0.211
AC:
1817
ExAC
AF:
0.241
AC:
29264
Asia WGS
AF:
0.257
AC:
898
AN:
3478
EpiCase
AF:
0.203
EpiControl
AF:
0.204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
20
DANN
Benign
0.90
DEOGEN2
Benign
0.010
T;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.15
T;T
MetaRNN
Benign
0.0037
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.54
N;N
REVEL
Benign
0.11
Sift
Benign
0.34
T;T
Sift4G
Benign
0.32
T;T
Polyphen
0.0
B;B
Vest4
0.010
MPC
0.21
ClinPred
0.019
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.035
gMVP
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs25689; hg19: chr9-74360096; COSMIC: COSV65486134; COSMIC: COSV65486134; API