8-70589239-A-C

Variant names:

• chr8-70589239-A-C
• rs7011101
• NM_014294.6:c.571-2063T>G

Variant summary

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

The NM_014294.6(TRAM1):​c.571-2063T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,226 control chromosomes in the GnomAD database, including 1,324 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 0.12 (1324 hom., cov: 32)
• Consequence: TRAM1 NM_014294.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 9 publications found

Genes affected

TRAM1 (HGNC:20568): (translocation associated membrane protein 1) This gene encodes a multi-pass membrane protein that is part of the mammalian endoplasmic reticulum. The encoded protein influences glycosylation and facilitates the translocation of secretory proteins across the endoplasmic reticulum membrane by regulating which domains of the nascent polypeptide chain are visible to the cytosol during a translocational pause. [provided by RefSeq, Oct 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAM1	NM_014294.6	c.571-2063T>G		intron_variant	Intron 6 of 10	ENST00000262213.7	NP_055109.1
TRAM1	NM_001317804.2	c.478-2063T>G		intron_variant	Intron 7 of 11		NP_001304733.1
TRAM1	NM_001317805.2	c.313-2063T>G		intron_variant	Intron 6 of 10		NP_001304734.1
TRAM1	XM_047421636.1	c.313-2063T>G		intron_variant	Intron 7 of 11		XP_047277592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAM1	ENST00000262213.7	c.571-2063T>G		intron_variant	Intron 6 of 10	1	NM_014294.6	ENSP00000262213.2
TRAM1	ENST00000521425.5	c.313-2063T>G		intron_variant	Intron 6 of 10	2		ENSP00000428052.1
TRAM1	ENST00000521049.5	n.445-1559T>G		intron_variant	Intron 3 of 6	5

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18527 AN: 152108 Hom.: 1319 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0138

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.122 AC: 18541 AN: 152226 Hom.: 1324 Cov.: 32 AF XY: 0.118 AC XY: 8760 AN XY: 74440

African (AFR) AF: 0.187 AC: 7764 AN: 41502

American (AMR) AF: 0.122 AC: 1871 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5188

South Asian (SAS) AF: 0.103 AC: 498 AN: 4822

European-Finnish (FIN) AF: 0.0463 AC: 491 AN: 10610

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6851 AN: 68018

Other (OTH) AF: 0.113 AC: 239 AN: 2116

Alfa AF: 0.111 Hom.: 155

Bravo AF: 0.128

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.23
PhyloP100		3.0
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: rs7011101; hg19: chr8-71501474;