chr9-71685395-T-TA

Position:

• chr9-71685395-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013390.3(CEMIP2):​c.3956-3_3956-2insT 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 ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (15260 hom., cov: 0)
  • Exomes 𝑓: 0.37 (1402 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEMIP2 NM_013390.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 9-71685395-T-TA is Benign according to our data. Variant chr9-71685395-T-TA is described in ClinVar as [Benign]. Clinvar id is 403552.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEMIP2	NM_013390.3	c.3956-3_3956-2insT		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.3956-3_3956-2insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_013390.3	P1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 59779 AN: 116292 Hom.: 15272 Cov.: 0

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.541

GnomAD3 exomes AF: 0.248 AC: 4399 AN: 17724 Hom.: 276 AF XY: 0.235 AC XY: 2212 AN XY: 9410

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.334

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.285

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.371 AC: 387930 AN: 1044974 Hom.: 1402 Cov.: 14 AF XY: 0.370 AC XY: 184881 AN XY: 499412

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.514 AC: 59754 AN: 116268 Hom.: 15260 Cov.: 0 AF XY: 0.509 AC XY: 27533 AN XY: 54044

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.536

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;