rs2274699

Variant names:

• chr9-71735116-T-G
• rs2274699
• NM_013390.3:c.1205-122A>C

Variant summary

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

The NM_013390.3(CEMIP2):​c.1205-122A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 1,135,274 control chromosomes in the GnomAD database, including 4,693 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 0.071 (543 hom., cov: 31)
  • Exomes 𝑓: 0.086 (4150 hom.)
• Consequence: CEMIP2 NM_013390.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 2 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 (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 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.1205-122A>C		intron	N/A	NP_037522.1
	CEMIP2	NM_001135820.2		c.1205-2596A>C		intron	N/A	NP_001129292.1
	CEMIP2	NM_001349784.2		c.-676-122A>C		intron	N/A	NP_001336713.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP2	ENST00000377044.9	TSL:1 MANE Select	c.1205-122A>C		intron	N/A	ENSP00000366243.4
	CEMIP2	ENST00000377066.9	TSL:1	c.1205-2596A>C		intron	N/A	ENSP00000366266.5
	CEMIP2	ENST00000542935.5	TSL:1	n.1205-122A>C		intron	N/A	ENSP00000437750.1

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10750 AN: 151954 Hom.: 543 Cov.: 31

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.0623

GnomAD4 exome AF: 0.0864 AC: 84981 AN: 983202 Hom.: 4150 AF XY: 0.0896 AC XY: 43816 AN XY: 489226

African (AFR) AF: 0.0420 AC: 942 AN: 22450

American (AMR) AF: 0.0429 AC: 870 AN: 20294

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 542 AN: 17074

East Asian (EAS) AF: 0.0437 AC: 1490 AN: 34082

South Asian (SAS) AF: 0.189 AC: 10395 AN: 54868

European-Finnish (FIN) AF: 0.0961 AC: 3069 AN: 31924

Middle Eastern (MID) AF: 0.0744 AC: 272 AN: 3656

European-Non Finnish (NFE) AF: 0.0848 AC: 64009 AN: 755188

Other (OTH) AF: 0.0777 AC: 3392 AN: 43666

GnomAD4 genome AF: 0.0707 AC: 10758 AN: 152072 Hom.: 543 Cov.: 31 AF XY: 0.0734 AC XY: 5459 AN XY: 74336

African (AFR) AF: 0.0392 AC: 1627 AN: 41478

American (AMR) AF: 0.0460 AC: 704 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3468

East Asian (EAS) AF: 0.0207 AC: 107 AN: 5170

South Asian (SAS) AF: 0.193 AC: 929 AN: 4802

European-Finnish (FIN) AF: 0.110 AC: 1157 AN: 10554

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5915 AN: 67992

Other (OTH) AF: 0.0659 AC: 139 AN: 2110

Alfa AF: 0.0866 Hom.: 474

Bravo AF: 0.0602

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.096
DANN	Benign	0.35
PhyloP100		-1.0
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: rs2274699; hg19: chr9-74350032;