rs6756470

Variant names:

• chr2-191954304-C-T
• rs6756470
• NM_016192.4:c.870-467G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEFF2	NM_016192.4	c.870-467G>A		intron_variant	Intron 8 of 9	ENST00000272771.10	NP_057276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEFF2	ENST00000272771.10	c.870-467G>A		intron_variant	Intron 8 of 9	1	NM_016192.4	ENSP00000272771.5

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

African (AFR) AF: 0.272 AC: 11250 AN: 41374

American (AMR) AF: 0.249 AC: 3799 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 938 AN: 3464

East Asian (EAS) AF: 0.0669 AC: 345 AN: 5158

South Asian (SAS) AF: 0.165 AC: 789 AN: 4782

European-Finnish (FIN) AF: 0.250 AC: 2632 AN: 10542

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19504 AN: 67884

Other (OTH) AF: 0.242 AC: 512 AN: 2114

Alfa AF: 0.280 Hom.: 3436

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
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs6756470; hg19: chr2-192819030;