9-71685724-A-G

Variant names:

• chr9-71685724-A-G
• rs2310021
• NM_013390.3:c.3955+19T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013390.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP2	NM_013390.3	MANE Select	c.3955+19T>C		intron	N/A	NP_037522.1	Q9UHN6-1
	CEMIP2	NM_001135820.2		c.3766+19T>C		intron	N/A	NP_001129292.1	Q9UHN6-2
	CEMIP2	NM_001349784.2		c.2041+19T>C		intron	N/A	NP_001336713.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEMIP2	ENST00000377044.9	TSL:1 MANE Select	c.3955+19T>C		intron	N/A	ENSP00000366243.4	Q9UHN6-1
	CEMIP2	ENST00000377066.9	TSL:1	c.3766+19T>C		intron	N/A	ENSP00000366266.5	Q9UHN6-2
	CEMIP2	ENST00000538669.1	TSL:1	n.1686+19T>C		intron	N/A

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

GnomAD2 exomes AF: 0.816 AC: 203736 AN: 249710 AF XY: 0.805

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 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

African (AFR) AF: 0.937 AC: 31046 AN: 33142

American (AMR) AF: 0.888 AC: 39575 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 18530 AN: 26000

East Asian (EAS) AF: 0.998 AC: 39505 AN: 39580

South Asian (SAS) AF: 0.800 AC: 68571 AN: 85760

European-Finnish (FIN) AF: 0.774 AC: 41268 AN: 53308

Middle Eastern (MID) AF: 0.731 AC: 4195 AN: 5738

European-Non Finnish (NFE) AF: 0.764 AC: 838192 AN: 1097706

Other (OTH) AF: 0.791 AC: 47320 AN: 59830

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

African (AFR) AF: 0.933 AC: 38756 AN: 41552

American (AMR) AF: 0.843 AC: 12884 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2473 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5149 AN: 5178

South Asian (SAS) AF: 0.819 AC: 3941 AN: 4814

European-Finnish (FIN) AF: 0.776 AC: 8205 AN: 10570

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52297 AN: 67984

Other (OTH) AF: 0.809 AC: 1711 AN: 2114

Alfa AF: 0.782 Hom.: 82703

Bravo AF: 0.841

Asia WGS AF: 0.916 AC: 3183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.59
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2310021; hg19: chr9-74300640;