9-71745293-G-C

Variant names:

• chr9-71745293-G-C
• rs3739783
• NM_013390.3:c.759C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013390.3(CEMIP2):​c.759C>G​(p.Pro253Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,844 control chromosomes in the GnomAD database, including 15,717 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1253 hom., cov: 31)
  • Exomes 𝑓: 0.14 (14464 hom.)
• Consequence: CEMIP2 NM_013390.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550
• Publications: 10 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=0.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP2	NM_013390.3	c.759C>G	p.Pro253Pro	synonymous_variant	Exon 4 of 24	ENST00000377044.9	NP_037522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP2	ENST00000377044.9	c.759C>G	p.Pro253Pro	synonymous_variant	Exon 4 of 24	1	NM_013390.3	ENSP00000366243.4
CEMIP2	ENST00000377066.9	c.759C>G	p.Pro253Pro	synonymous_variant	Exon 4 of 23	1		ENSP00000366266.5
CEMIP2	ENST00000542935.5	n.759C>G		non_coding_transcript_exon_variant	Exon 4 of 24	1		ENSP00000437750.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17745 AN: 151994 Hom.: 1248 Cov.: 31

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.145 AC: 36315 AN: 251222 AF XY: 0.145

Gnomad AFR exome AF: 0.0447

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.134

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.138 AC: 201326 AN: 1461732 Hom.: 14464 Cov.: 34 AF XY: 0.138 AC XY: 100372 AN XY: 727132

African (AFR) AF: 0.0387 AC: 1297 AN: 33478

American (AMR) AF: 0.191 AC: 8524 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 3635 AN: 26136

East Asian (EAS) AF: 0.141 AC: 5614 AN: 39688

South Asian (SAS) AF: 0.150 AC: 12951 AN: 86258

European-Finnish (FIN) AF: 0.181 AC: 9657 AN: 53412

Middle Eastern (MID) AF: 0.103 AC: 593 AN: 5768

European-Non Finnish (NFE) AF: 0.136 AC: 151079 AN: 1111882

Other (OTH) AF: 0.132 AC: 7976 AN: 60390

GnomAD4 genome AF: 0.117 AC: 17748 AN: 152112 Hom.: 1253 Cov.: 31 AF XY: 0.121 AC XY: 9007 AN XY: 74348

African (AFR) AF: 0.0456 AC: 1892 AN: 41498

American (AMR) AF: 0.164 AC: 2505 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.157 AC: 813 AN: 5168

South Asian (SAS) AF: 0.159 AC: 764 AN: 4818

European-Finnish (FIN) AF: 0.185 AC: 1956 AN: 10566

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8996 AN: 68004

Other (OTH) AF: 0.113 AC: 239 AN: 2114

Alfa AF: 0.127 Hom.: 426

Bravo AF: 0.111

Asia WGS AF: 0.128 AC: 444 AN: 3478

EpiCase AF: 0.127

EpiControl AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		0.55
Mutation Taster		=100/0	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: rs3739783; hg19: chr9-74360209; COSMIC: COSV65486151; COSMIC: COSV65486151;