rs6756470

Positions:

• chr2-191954304-C-T

Variant summary

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

The NM_016192.4(TMEFF2):​c.870-467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,768 control chromosomes in the GnomAD database, including 5,423 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 0.26 (5423 hom., cov: 31)
• Consequence: TMEFF2 NM_016192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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]

CAVIN2-AS1 (HGNC:40517): (CAVIN2 and TMEFF2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEFF2	NM_016192.4	c.870-467G>A		intron_variant		ENST00000272771.10
TMEFF2	NM_001305134.2	c.870-467G>A		intron_variant
TMEFF2	XM_011510890.4	c.843-467G>A		intron_variant
TMEFF2	XM_017003739.3	c.843-467G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEFF2	ENST00000272771.10	c.870-467G>A		intron_variant		1	NM_016192.4	P1
TMEFF2	ENST00000392314.5	c.870-467G>A		intron_variant		1
CAVIN2-AS1	ENST00000424116.7	n.239-80390C>T		intron_variant, non_coding_transcript_variant		2
CAVIN2-AS1	ENST00000428980.6	n.499+31260C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40094 AN: 151650 Hom.: 5420 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0663

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.264 AC: 40124 AN: 151768 Hom.: 5423 Cov.: 31 AF XY: 0.259 AC XY: 19230 AN XY: 74164

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.0669

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.242

Alfa AF: 0.279 Hom.: 2198

Bravo AF: 0.266

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.71

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: rs6756470; hg19: chr2-192819030;