rs2274699

chr9-71735116-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEMIP2	NM_013390.3	c.1205-122A>C		intron_variant		ENST00000377044.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEMIP2	ENST00000377044.9	c.1205-122A>C		intron_variant		1	NM_013390.3	P1
CEMIP2	ENST00000377066.9	c.1205-2596A>C		intron_variant		1
CEMIP2	ENST00000542935.5	c.1205-122A>C		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR exome AF: 0.0420

Gnomad4 AMR exome AF: 0.0429

Gnomad4 ASJ exome AF: 0.0317

Gnomad4 EAS exome AF: 0.0437

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.0961

Gnomad4 NFE exome AF: 0.0848

Gnomad4 OTH exome AF: 0.0777

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

Gnomad4 AFR AF: 0.0392

Gnomad4 AMR AF: 0.0460

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0207

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0913 Hom.: 369

Bravo AF: 0.0602

Asia WGS AF: 0.101 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.096
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs2274699; hg19: chr9-74350032;