rs3738882

Variant names:

• chr2-192184169-C-G
• rs3738882
• NM_016192.4:c.412+185G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-192184169-C-G
• chr2-192184169-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016192.4(TMEFF2):​c.412+185G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,954 control chromosomes in the GnomAD database, including 31,705 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 0.64 (31705 hom., cov: 33)
• Consequence: TMEFF2 NM_016192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEFF2	NM_016192.4	c.412+185G>C		intron_variant	Intron 3 of 9	ENST00000272771.10	NP_057276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEFF2	ENST00000272771.10	c.412+185G>C		intron_variant	Intron 3 of 9	1	NM_016192.4	ENSP00000272771.5
TMEFF2	ENST00000392314.5	c.412+185G>C		intron_variant	Intron 3 of 9	1		ENSP00000376128.1
TMEFF2	ENST00000409056.3	c.412+185G>C		intron_variant	Intron 3 of 3	1		ENSP00000386871.3

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97866 AN: 151836 Hom.: 31679 Cov.: 33

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.645 AC: 97944 AN: 151954 Hom.: 31705 Cov.: 33 AF XY: 0.646 AC XY: 48036 AN XY: 74306

African (AFR) AF: 0.618 AC: 25598 AN: 41444

American (AMR) AF: 0.638 AC: 9724 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2179 AN: 3460

East Asian (EAS) AF: 0.639 AC: 3298 AN: 5158

South Asian (SAS) AF: 0.587 AC: 2827 AN: 4820

European-Finnish (FIN) AF: 0.752 AC: 7963 AN: 10592

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44184 AN: 67924

Other (OTH) AF: 0.624 AC: 1316 AN: 2108

Alfa AF: 0.652 Hom.: 3865

Bravo AF: 0.636

Asia WGS AF: 0.665 AC: 2315 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	3.4
DANN	Benign	0.58
PhyloP100		-0.38
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: rs3738882; hg19: chr2-193048895; COSMIC: COSV55829751;