9-71685395-TAAAAAAA-TAAAAAA

Position:

• chr9-71685395-TAAAAAAA-TAAAAAA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_013390.3(CEMIP2):​c.3956-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.040 (82 hom., cov: 0)
  • Exomes 𝑓: 0.066 (5 hom.)
• Consequence: CEMIP2 NM_013390.3 splice_region, splice_polypyrimidine_tract, 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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 9-71685395-TA-T is Benign according to our data. Variant chr9-71685395-TA-T is described in Lovd as [Benign]. Variant chr9-71685395-TA-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 4650 AN: 116296 Hom.: 82 Cov.: 0

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0244

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0613

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0579

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0431

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.0365

GnomAD3 exomes AF: 0.119 AC: 2101 AN: 17724 Hom.: 0 AF XY: 0.126 AC XY: 1186 AN XY: 9410

Gnomad AFR exome AF: 0.0419

Gnomad AMR exome AF: 0.0916

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.0309

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.0656 AC: 68356 AN: 1042664 Hom.: 5 Cov.: 14 AF XY: 0.0661 AC XY: 32916 AN XY: 498126

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0454

Gnomad4 ASJ exome AF: 0.0796

Gnomad4 EAS exome AF: 0.00572

Gnomad4 SAS exome AF: 0.0804

Gnomad4 FIN exome AF: 0.0616

Gnomad4 NFE exome AF: 0.0685

Gnomad4 OTH exome AF: 0.0607

GnomAD4 genome AF: 0.0400 AC: 4650 AN: 116272 Hom.: 82 Cov.: 0 AF XY: 0.0393 AC XY: 2127 AN XY: 54054

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0613

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0586

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0580

Gnomad4 OTH AF: 0.0363

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs36080695; hg19: chr9-74300311;