chr8-108647860-A-G

Position:

• chr8-108647860-A-G

Variant summary

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

The ENST00000518838.1(TMEM74):​n.264+7433T>C 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 0.43 in 151,396 control chromosomes in the GnomAD database, including 15,734 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 0.43 (15734 hom., cov: 31)
• Consequence: TMEM74 ENST00000518838.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM74	NR_136411.2	n.264+7433T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM74	ENST00000518838.1	n.264+7433T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 64967 AN: 151278 Hom.: 15688 Cov.: 31

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.430 AC: 65073 AN: 151396 Hom.: 15734 Cov.: 31 AF XY: 0.430 AC XY: 31823 AN XY: 73950

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.415

Alfa AF: 0.323 Hom.: 9895

Bravo AF: 0.457

Asia WGS AF: 0.568 AC: 1973 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.6
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2935762; hg19: chr8-109660089;