9-71745180-C-T

Variant names:

• chr9-71745180-C-T
• rs25689
• NM_013390.3:c.872G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5343 hom., cov: 31)
  • Exomes 𝑓: 0.23 (39149 hom.)
• Consequence: CEMIP2 NM_013390.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP2	NM_013390.3	MANE Select	c.872G>A	p.Arg291His	missense	Exon 4 of 24	NP_037522.1
	CEMIP2	NM_001135820.2		c.872G>A	p.Arg291His	missense	Exon 4 of 23	NP_001129292.1
	CEMIP2	NM_001349784.2		c.-1009G>A		5_prime_UTR	Exon 4 of 24	NP_001336713.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP2	ENST00000377044.9	TSL:1 MANE Select	c.872G>A	p.Arg291His	missense	Exon 4 of 24	ENSP00000366243.4
	CEMIP2	ENST00000377066.9	TSL:1	c.872G>A	p.Arg291His	missense	Exon 4 of 23	ENSP00000366266.5
	CEMIP2	ENST00000542935.5	TSL:1	n.872G>A		non_coding_transcript_exon	Exon 4 of 24	ENSP00000437750.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38804 AN: 151814 Hom.: 5328 Cov.: 31

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

GnomAD2 exomes AF: 0.240 AC: 60214 AN: 251268 AF XY: 0.242

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 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

African (AFR) AF: 0.332 AC: 11121 AN: 33478

American (AMR) AF: 0.238 AC: 10648 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4433 AN: 26136

East Asian (EAS) AF: 0.181 AC: 7198 AN: 39696

South Asian (SAS) AF: 0.341 AC: 29377 AN: 86258

European-Finnish (FIN) AF: 0.275 AC: 14684 AN: 53420

Middle Eastern (MID) AF: 0.183 AC: 1057 AN: 5768

European-Non Finnish (NFE) AF: 0.216 AC: 240096 AN: 1111986

Other (OTH) AF: 0.226 AC: 13660 AN: 60394

GnomAD4 genome AF: 0.256 AC: 38860 AN: 151932 Hom.: 5343 Cov.: 31 AF XY: 0.261 AC XY: 19381 AN XY: 74256

African (AFR) AF: 0.334 AC: 13816 AN: 41418

American (AMR) AF: 0.242 AC: 3690 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 571 AN: 3470

East Asian (EAS) AF: 0.176 AC: 912 AN: 5182

South Asian (SAS) AF: 0.351 AC: 1689 AN: 4810

European-Finnish (FIN) AF: 0.291 AC: 3065 AN: 10534

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14421 AN: 67950

Other (OTH) AF: 0.237 AC: 500 AN: 2106

Alfa AF: 0.220 Hom.: 14227

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 v4.9

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
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.9
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.11
Sift	Benign	0.34	T
Sift4G	Benign	0.32	T
Polyphen		0.0	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
Mutation Taster		=88/12	polymorphism (auto)

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

Other links and lift over

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