chr6-52575061-C-T

Variant names:

• chr6-52575061-C-T
• rs1883931
• NM_012288.4:c.120+1735G>A

Variant summary

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

The NM_012288.4(TRAM2):​c.120+1735G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,066 control chromosomes in the GnomAD database, including 4,506 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 0.24 (4506 hom., cov: 32)
• Consequence: TRAM2 NM_012288.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAM2	NM_012288.4	c.120+1735G>A		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.120+1735G>A		intron_variant	Intron 1 of 10	1	NM_012288.4	ENSP00000182527.3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36446 AN: 151948 Hom.: 4500 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.240 AC: 36469 AN: 152066 Hom.: 4506 Cov.: 32 AF XY: 0.239 AC XY: 17791 AN XY: 74334

African (AFR) AF: 0.197 AC: 8187 AN: 41484

American (AMR) AF: 0.172 AC: 2627 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3472

East Asian (EAS) AF: 0.133 AC: 688 AN: 5172

South Asian (SAS) AF: 0.218 AC: 1052 AN: 4822

European-Finnish (FIN) AF: 0.297 AC: 3136 AN: 10562

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19285 AN: 67962

Other (OTH) AF: 0.211 AC: 447 AN: 2114

Alfa AF: 0.262 Hom.: 16159

Bravo AF: 0.226

Asia WGS AF: 0.219 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.60
PhyloP100		-1.2
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: rs1883931; hg19: chr6-52439859; COSMIC: COSV51733210; COSMIC: COSV51733210;