rs1404192

chr9-71795531-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000545719.1(CEMIP2):c.-13+19424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 152,208 control chromosomes in the GnomAD database, including 236 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 0.034 (236 hom., cov: 32)
• Consequence: CEMIP2 ENST00000545719.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEMIP2	ENST00000545719.1	c.-13+19424A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5226 AN: 152090 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00911

Gnomad FIN AF: 0.00593

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00459

Gnomad OTH AF: 0.0292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0345 AC: 5245 AN: 152208 Hom.: 236 Cov.: 32 AF XY: 0.0327 AC XY: 2437 AN XY: 74416

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.00593

Gnomad4 NFE AF: 0.00459

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0256 Hom.: 23

Bravo AF: 0.0392

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.27
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1404192; hg19: chr9-74410447;