chr8-108647860-A-G

Variant names:

• chr8-108647860-A-G
• rs2935762
• ENST00000518838.1:n.264+7433T>C

Variant summary

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

The ENST00000518838.1(TMEM74):​n.264+7433T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 4 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]

LOC124902049 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LOC124902049		n.108647860A>G		intragenic_variant
TMEM74	NR_136411.2	n.264+7433T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM74	ENST00000518838.1	n.264+7433T>C		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.635 AC: 26136 AN: 41162

American (AMR) AF: 0.461 AC: 7000 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1083 AN: 3460

East Asian (EAS) AF: 0.711 AC: 3599 AN: 5062

South Asian (SAS) AF: 0.367 AC: 1765 AN: 4804

European-Finnish (FIN) AF: 0.310 AC: 3260 AN: 10532

Middle Eastern (MID) AF: 0.355 AC: 103 AN: 290

European-Non Finnish (NFE) AF: 0.310 AC: 21064 AN: 67880

Other (OTH) AF: 0.415 AC: 873 AN: 2106

Alfa AF: 0.328 Hom.: 11969

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
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs2935762; hg19: chr8-109660089;