rs714171

Variant names:

• chr6-52548920-C-A
• rs714171
• NM_012288.4:c.121-13074G>T

Variant summary

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

The NM_012288.4(TRAM2):​c.121-13074G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 152,244 control chromosomes in the GnomAD database, including 150 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 0.037 (150 hom., cov: 33)
• Consequence: TRAM2 NM_012288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• Publications: 1 publications found

Genes affected

TRAM2 (HGNC:16855): (translocation associated membrane protein 2) TRAM2 is a component of the translocon, a gated macromolecular channel that controls the posttranslational processing of nascent secretory and membrane proteins at the endoplasmic reticulum (ER) membrane.[supplied by OMIM, Jul 2004]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAM2	NM_012288.4	c.121-13074G>T		intron_variant	Intron 1 of 10	ENST00000182527.4	NP_036420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAM2	ENST00000182527.4	c.121-13074G>T		intron_variant	Intron 1 of 10	1	NM_012288.4	ENSP00000182527.3

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5651 AN: 152126 Hom.: 150 Cov.: 33

Gnomad AFR AF: 0.00869

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.0387

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

GnomAD4 genome AF: 0.0371 AC: 5650 AN: 152244 Hom.: 150 Cov.: 33 AF XY: 0.0368 AC XY: 2740 AN XY: 74444

African (AFR) AF: 0.00867 AC: 360 AN: 41530

American (AMR) AF: 0.0362 AC: 554 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3468

East Asian (EAS) AF: 0.00540 AC: 28 AN: 5182

South Asian (SAS) AF: 0.0527 AC: 254 AN: 4824

European-Finnish (FIN) AF: 0.0439 AC: 465 AN: 10604

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3595 AN: 68020

Other (OTH) AF: 0.0388 AC: 82 AN: 2116

Alfa AF: 0.0325 Hom.: 41

Bravo AF: 0.0346

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-0.81
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: rs714171; hg19: chr6-52413718;