rs12612396

Variant names:

• chr2-191967055-G-A
• rs12612396
• NM_016192.4:c.746-10677C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-191967055-G-A
• chr2-191967055-G-C
• chr2-191967055-G-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.746-10677C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,698 control chromosomes in the GnomAD database, including 46,347 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 0.78 (46347 hom., cov: 30)
• Consequence: TMEFF2 NM_016192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• 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]

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEFF2	NM_016192.4	MANE Select	c.746-10677C>T		intron	N/A	NP_057276.2
	TMEFF2	NM_001305134.2		c.746-10677C>T		intron	N/A	NP_001292063.1	Q9UIK5-2
	CAVIN2-AS1	NR_187184.1		n.285-67639G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEFF2	ENST00000272771.10	TSL:1 MANE Select	c.746-10677C>T		intron	N/A	ENSP00000272771.5	Q9UIK5-1
	TMEFF2	ENST00000392314.5	TSL:1	c.746-10677C>T		intron	N/A	ENSP00000376128.1	Q9UIK5-2
	TMEFF2	ENST00000877060.1		c.788-10677C>T		intron	N/A	ENSP00000547119.1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118420 AN: 151582 Hom.: 46308 Cov.: 30

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.781 AC: 118512 AN: 151698 Hom.: 46347 Cov.: 30 AF XY: 0.786 AC XY: 58313 AN XY: 74160

African (AFR) AF: 0.786 AC: 32512 AN: 41364

American (AMR) AF: 0.784 AC: 11947 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2561 AN: 3466

East Asian (EAS) AF: 0.937 AC: 4845 AN: 5172

South Asian (SAS) AF: 0.843 AC: 4060 AN: 4816

European-Finnish (FIN) AF: 0.807 AC: 8430 AN: 10448

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51610 AN: 67872

Other (OTH) AF: 0.793 AC: 1675 AN: 2112

Alfa AF: 0.768 Hom.: 11526

Bravo AF: 0.777

Asia WGS AF: 0.868 AC: 2984 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.2
DANN	Benign	0.21
PhyloP100		0.023
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: rs12612396; hg19: chr2-192831781;