9-71685395-TAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant names:

• chr9-71685395-TA-T
• rs36080695
• NM_013390.3:c.3956-3delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_013390.3(CEMIP2):​c.3956-3delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.040 (82 hom., cov: 0)
  • Exomes 𝑓: 0.066 (5 hom.)
• Consequence: CEMIP2 NM_013390.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 3 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEMIP2	NM_013390.3	c.3956-3delT		splice_region_variant, intron_variant	Intron 23 of 23	ENST00000377044.9	NP_037522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEMIP2	ENST00000377044.9	c.3956-3delT		splice_region_variant, intron_variant	Intron 23 of 23	1	NM_013390.3	ENSP00000366243.4

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 4650 AN: 116296 Hom.: 82 Cov.: 0

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.0244

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0613

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0579

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0431

Gnomad NFE AF: 0.0580

Gnomad OTH AF: 0.0365

GnomAD2 exomes AF: 0.119 AC: 2101 AN: 17724 AF XY: 0.126

Gnomad AFR exome AF: 0.0419

Gnomad AMR exome AF: 0.0916

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.0309

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.0656 AC: 68356 AN: 1042664 Hom.: 5 Cov.: 14 AF XY: 0.0661 AC XY: 32916 AN XY: 498126

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0116 AC: 256 AN: 22000

American (AMR) AF: 0.0454 AC: 513 AN: 11294

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 1166 AN: 14640

East Asian (EAS) AF: 0.00572 AC: 147 AN: 25692

South Asian (SAS) AF: 0.0804 AC: 2475 AN: 30778

European-Finnish (FIN) AF: 0.0616 AC: 1451 AN: 23574

Middle Eastern (MID) AF: 0.0678 AC: 195 AN: 2876

European-Non Finnish (NFE) AF: 0.0685 AC: 59581 AN: 869412

Other (OTH) AF: 0.0607 AC: 2572 AN: 42398

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0400 AC: 4650 AN: 116272 Hom.: 82 Cov.: 0 AF XY: 0.0393 AC XY: 2127 AN XY: 54054

African (AFR) AF: 0.0105 AC: 308 AN: 29280

American (AMR) AF: 0.0248 AC: 264 AN: 10656

Ashkenazi Jewish (ASJ) AF: 0.0613 AC: 189 AN: 3082

East Asian (EAS) AF: 0.00 AC: 0 AN: 4194

South Asian (SAS) AF: 0.0586 AC: 204 AN: 3484

European-Finnish (FIN) AF: 0.0439 AC: 165 AN: 3756

Middle Eastern (MID) AF: 0.0476 AC: 10 AN: 210

European-Non Finnish (NFE) AF: 0.0580 AC: 3434 AN: 59250

Other (OTH) AF: 0.0363 AC: 56 AN: 1542

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs36080695; hg19: chr9-74300311;