rs2935776

Positions:

• chr8-108617674-A-G
• chr8-108617674-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521504.1(ENSG00000253949):​n.171-8882A>G variant causes a intron, non coding transcript 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: ENST00000521504.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM74	NR_136411.2	n.265-8848T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM74	ENST00000518838.1	n.265-8848T>C		intron_variant, non_coding_transcript_variant		1
	ENST00000521504.1	n.171-8882A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.201

Alfa AF: 0.216 Hom.: 5530

Bravo AF: 0.220

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2935776; hg19: chr8-109629903;