9-71685724-A-G

Position:

• chr9-71685724-A-G

Variant summary

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

The NM_013390.3(CEMIP2):​c.3955+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,597,780 control chromosomes in the GnomAD database, including 495,534 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 0.83 (52976 hom., cov: 32)
  • Exomes 𝑓: 0.78 (442558 hom.)
• Consequence: CEMIP2 NM_013390.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEMIP2	NM_013390.3	c.3955+19T>C		intron_variant		ENST00000377044.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEMIP2	ENST00000377044.9	c.3955+19T>C		intron_variant		1	NM_013390.3	P1

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126239 AN: 152046 Hom.: 52920 Cov.: 32

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.807

GnomAD3 exomes AF: 0.816 AC: 203736 AN: 249710 Hom.: 83976 AF XY: 0.805 AC XY: 108670 AN XY: 134928

Gnomad AFR exome AF: 0.935

Gnomad AMR exome AF: 0.894

Gnomad ASJ exome AF: 0.714

Gnomad EAS exome AF: 0.997

Gnomad SAS exome AF: 0.808

Gnomad FIN exome AF: 0.781

Gnomad NFE exome AF: 0.765

Gnomad OTH exome AF: 0.790

GnomAD4 exome AF: 0.780 AC: 1128202 AN: 1445616 Hom.: 442558 Cov.: 26 AF XY: 0.779 AC XY: 561310 AN XY: 720160

Gnomad4 AFR exome AF: 0.937

Gnomad4 AMR exome AF: 0.888

Gnomad4 ASJ exome AF: 0.713

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.764

Gnomad4 OTH exome AF: 0.791

GnomAD4 genome AF: 0.830 AC: 126352 AN: 152164 Hom.: 52976 Cov.: 32 AF XY: 0.831 AC XY: 61767 AN XY: 74368

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.809

Alfa AF: 0.776 Hom.: 65028

Bravo AF: 0.841

Asia WGS AF: 0.916 AC: 3183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2310021; hg19: chr9-74300640;