9-71685395-TAAAAAAA-TAAAAAAAAA

Position:

• chr9-71685395-TAAAAAAA-TAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_013390.3(CEMIP2):​c.3956-4_3956-3dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5271 hom., cov: 0)
  • Exomes 𝑓: 0.22 (437 hom.)
• Consequence: CEMIP2 NM_013390.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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]

CEMIP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEMIP2	NM_013390.3	c.3956-4_3956-3dupTT		splice_region_variant, intron_variant		ENST00000377044.9	NP_037522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEMIP2	ENST00000377044.9	c.3956-4_3956-3dupTT		splice_region_variant, intron_variant		1	NM_013390.3	ENSP00000366243.4

Frequencies

GnomAD3 genomes AF: 0.274 AC: 31835 AN: 116034 Hom.: 5270 Cov.: 0

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.164

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.125 AC: 2216 AN: 17724 Hom.: 92 AF XY: 0.123 AC XY: 1162 AN XY: 9410

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.0945

Gnomad EAS exome AF: 0.245

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.0703

Gnomad NFE exome AF: 0.0860

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.216 AC: 221365 AN: 1023208 Hom.: 437 Cov.: 14 AF XY: 0.215 AC XY: 105051 AN XY: 488860

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.274 AC: 31841 AN: 116010 Hom.: 5271 Cov.: 0 AF XY: 0.280 AC XY: 15100 AN XY: 53938

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs36080695; hg19: chr9-74300311;