rs4745122

chr9-71777771-A-Cchr9-71777771-A-Gchr9-71777771-A-T

Variant summary

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

The ENST00000545719.1(CEMIP2):c.-12-27386T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,010 control chromosomes in the GnomAD database, including 36,854 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 0.68 (36854 hom., cov: 31)
• Consequence: CEMIP2 ENST00000545719.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 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.-12-27386T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104044 AN: 151892 Hom.: 36840 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.685 AC: 104091 AN: 152010 Hom.: 36854 Cov.: 31 AF XY: 0.684 AC XY: 50816 AN XY: 74308

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.765

Gnomad4 OTH AF: 0.696

Alfa AF: 0.750 Hom.: 85745

Bravo AF: 0.678

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.24
Dann	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4745122; hg19: chr9-74392687;