rs13007495

Variant names:

• chr2-192090779-T-C
• rs13007495
• NM_016192.4:c.440-33004A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 = 0.153 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.440-33004A>G		intron	N/A	NP_057276.2
	TMEFF2	NM_001305134.2		c.440-33004A>G		intron	N/A	NP_001292063.1	Q9UIK5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEFF2	ENST00000272771.10	TSL:1 MANE Select	c.440-33004A>G		intron	N/A	ENSP00000272771.5	Q9UIK5-1
	TMEFF2	ENST00000392314.5	TSL:1	c.440-33004A>G		intron	N/A	ENSP00000376128.1	Q9UIK5-2
	TMEFF2	ENST00000877060.1		c.440-33004A>G		intron	N/A	ENSP00000547119.1

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

African (AFR) AF: 0.0240 AC: 996 AN: 41564

American (AMR) AF: 0.0787 AC: 1202 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0301 AC: 145 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1669 AN: 10598

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10584 AN: 67992

Other (OTH) AF: 0.0955 AC: 202 AN: 2116

Alfa AF: 0.129 Hom.: 3408

Bravo AF: 0.0895

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.50
PhyloP100		-0.66
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs13007495;

hg19: chr2-192955505;