10-104254967-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004832.3(GSTO1):c.34+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,607,418 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (37 hom.)
• Consequence: GSTO1 NM_004832.3 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.531

Genes affected

GSTO1 (HGNC:13312): (glutathione S-transferase omega 1) The protein encoded by this gene is an omega class glutathione S-transferase (GST) with glutathione-dependent thiol transferase and dehydroascorbate reductase activities. GSTs are involved in the metabolism of xenobiotics and carcinogens. The encoded protein acts as a homodimer and is found in the cytoplasm. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

LOC124902497 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-104254967-G-A is Benign according to our data. Variant chr10-104254967-G-A is described in ClinVar as [Benign]. Clinvar id is 782535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1851/152164) while in subpopulation AFR AF= 0.0424 (1762/41566). AF 95% confidence interval is 0.0407. There are 27 homozygotes in gnomad4. There are 892 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTO1	NM_004832.3	c.34+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000369713.10
LOC124902497	XR_007062284.1	n.366-6375C>T		intron_variant, non_coding_transcript_variant
GSTO1	NM_001191002.2	c.34+5G>A		splice_donor_5th_base_variant, intron_variant
GSTO1	NM_001191003.2	c.-50-196G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTO1	ENST00000369713.10	c.34+5G>A		splice_donor_5th_base_variant, intron_variant		1	NM_004832.3	P1

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1847 AN: 152046 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00297 AC: 687 AN: 231524 Hom.: 14 AF XY: 0.00230 AC XY: 291 AN XY: 126334

Gnomad AFR exome AF: 0.0448

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000290

Gnomad OTH exome AF: 0.000899

GnomAD4 exome AF: 0.00130 AC: 1896 AN: 1455254 Hom.: 37 Cov.: 31 AF XY: 0.00109 AC XY: 786 AN XY: 723598

Gnomad4 AFR exome AF: 0.0484

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000397

Gnomad4 OTH exome AF: 0.00241

GnomAD4 genome AF: 0.0122 AC: 1851 AN: 152164 Hom.: 27 Cov.: 32 AF XY: 0.0120 AC XY: 892 AN XY: 74386

Gnomad4 AFR AF: 0.0424

Gnomad4 AMR AF: 0.00444

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00567 Hom.: 14

Bravo AF: 0.0133

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	19
Dann	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.84		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.84		Position offset: -5

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

Publications

LitVar

Other links and lift over

dbSNP: rs629771; hg19: chr10-106014725;