rs13007495

chr2-192090779-T-C

Variant summary

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

The NM_016192.4(TMEFF2):c.440-33004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,232 control chromosomes in the GnomAD database, including 1,043 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 0.10 (1043 hom., cov: 32)
• Consequence: TMEFF2 NM_016192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

Genes affected

TMEFF2 (HGNC:11867): (transmembrane protein with EGF like and two follistatin like domains 2) This gene encodes a member of the tomoregulin family of transmembrane proteins. This protein has been shown to function as both an oncogene and a tumor suppressor depending on the cellular context and may regulate prostate cancer cell invasion. Multiple soluble forms of this protein have been identified that arise from both an alternative splice variant and ectodomain shedding. Additionally, this gene has been found to be hypermethylated in multiple cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEFF2	NM_016192.4	c.440-33004A>G		intron_variant		ENST00000272771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEFF2	ENST00000272771.10	c.440-33004A>G		intron_variant		1	NM_016192.4	P1
TMEFF2	ENST00000392314.5	c.440-33004A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15249 AN: 152114 Hom.: 1043 Cov.: 32

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.0969

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

GnomAD4 genome AF: 0.100 AC: 15240 AN: 152232 Hom.: 1043 Cov.: 32 AF XY: 0.0966 AC XY: 7189 AN XY: 74424

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0301

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.0955

Alfa AF: 0.139 Hom.: 2145

Bravo AF: 0.0895

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.6
Dann	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs13007495; hg19: chr2-192955505;