8-108714274-A-G

Variant names:

• chr8-108714274-A-G
• rs1391200
• ENST00000518838.1:n.120-58837T>C

Variant summary

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

The ENST00000518838.1(TMEM74):​n.120-58837T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,044 control chromosomes in the GnomAD database, including 10,678 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 0.37 (10678 hom., cov: 32)
• Consequence: TMEM74 ENST00000518838.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 2 publications found

Genes affected

TMEM74 (HGNC:26409): (transmembrane protein 74) Involved in macroautophagy. Predicted to be located in autophagosome membrane; cytoplasmic vesicle; and lysosomal membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000308266 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM74	NR_136411.2	n.120-58837T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM74	ENST00000518838.1	n.120-58837T>C		intron_variant	Intron 1 of 3	1
ENSG00000308266	ENST00000832897.1	n.156+1077T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55616 AN: 151926 Hom.: 10649 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.366 AC: 55693 AN: 152044 Hom.: 10678 Cov.: 32 AF XY: 0.373 AC XY: 27692 AN XY: 74314

African (AFR) AF: 0.419 AC: 17368 AN: 41464

American (AMR) AF: 0.428 AC: 6541 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3108 AN: 5164

South Asian (SAS) AF: 0.359 AC: 1727 AN: 4814

European-Finnish (FIN) AF: 0.351 AC: 3713 AN: 10572

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21010 AN: 67962

Other (OTH) AF: 0.376 AC: 794 AN: 2110

Alfa AF: 0.325 Hom.: 14030

Bravo AF: 0.377

Asia WGS AF: 0.500 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.1
DANN	Benign	0.97
PhyloP100		-0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1391200; hg19: chr8-109726503;