rs36080695

chr9-71685395-TAAAAAAA-Tchr9-71685395-TAAAAAAA-TAchr9-71685395-TAAAAAAA-TAAchr9-71685395-TAAAAAAA-TAAAAchr9-71685395-TAAAAAAA-TAAAAAchr9-71685395-TAAAAAAA-TAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAchr9-71685395-TAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013390.3(CEMIP2):c.3956-9_3956-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000288 in 1,178,902 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: CEMIP2 NM_013390.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEMIP2	NM_013390.3	c.3956-9_3956-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000377044.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEMIP2	ENST00000377044.9	c.3956-9_3956-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_013390.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000859 AC: 1 AN: 116356 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000169

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000311 AC: 33 AN: 1062546 Hom.: 0 AF XY: 0.0000158 AC XY: 8 AN XY: 507886

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000361

Gnomad4 OTH exome AF: 0.0000231

GnomAD4 genome AF: 0.00000859 AC: 1 AN: 116356 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54086

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000169

Gnomad4 OTH AF: 0.00

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;