8-108617674-A-G

Variant names:

• chr8-108617674-A-G
• rs2935776
• ENST00000518838.1:n.265-8848T>C

Variant summary

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

The ENST00000518838.1(TMEM74):​n.265-8848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,964 control chromosomes in the GnomAD database, including 3,648 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 0.22 (3648 hom., cov: 31)
• Consequence: TMEM74 ENST00000518838.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 10 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]

ENSG00000253949 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518838.1. 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
	TMEM74	NR_136411.2		n.265-8848T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM74	ENST00000518838.1	TSL:1	n.265-8848T>C		intron	N/A
	ENSG00000253949	ENST00000521504.1	TSL:3	n.171-8882A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33111 AN: 151846 Hom.: 3641 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.218 AC: 33136 AN: 151964 Hom.: 3648 Cov.: 31 AF XY: 0.217 AC XY: 16088 AN XY: 74252

African (AFR) AF: 0.221 AC: 9146 AN: 41448

American (AMR) AF: 0.214 AC: 3265 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3462

East Asian (EAS) AF: 0.271 AC: 1396 AN: 5142

South Asian (SAS) AF: 0.139 AC: 670 AN: 4808

European-Finnish (FIN) AF: 0.214 AC: 2258 AN: 10574

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14878 AN: 67948

Other (OTH) AF: 0.201 AC: 425 AN: 2114

Alfa AF: 0.217 Hom.: 8716

Bravo AF: 0.220

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.85
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs2935776; hg19: chr8-109629903;