rs10516528

Variant names:

• chr4-105818436-G-T
• rs10516528
• NM_001370181.1:c.1241-4518G>T

Variant summary

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

The NM_001370181.1(GSTCD):​c.1241-4518G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 151,878 control chromosomes in the GnomAD database, including 250 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 0.054 (250 hom., cov: 32)
• Consequence: GSTCD NM_001370181.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 7 publications found

Genes affected

GSTCD (HGNC:25806): (glutathione S-transferase C-terminal domain containing) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

INTS12 (HGNC:25067): (integrator complex subunit 12) INTS12 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

GSTCD-AS1 (HGNC:41117): (GSTCD antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTCD	NM_001370181.1	c.1241-4518G>T		intron_variant	Intron 5 of 11	ENST00000515279.6	NP_001357110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTCD	ENST00000515279.6	c.1241-4518G>T		intron_variant	Intron 5 of 11	5	NM_001370181.1	ENSP00000422354.1
GSTCD	ENST00000394728.4	c.1241-4518G>T		intron_variant	Intron 5 of 11	5		ENSP00000378216.3

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8167 AN: 151760 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0767

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

GnomAD4 genome AF: 0.0538 AC: 8165 AN: 151878 Hom.: 250 Cov.: 32 AF XY: 0.0514 AC XY: 3814 AN XY: 74248

African (AFR) AF: 0.0411 AC: 1707 AN: 41526

American (AMR) AF: 0.0682 AC: 1038 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 282 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4816

European-Finnish (FIN) AF: 0.0318 AC: 337 AN: 10594

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0643 AC: 4358 AN: 67750

Other (OTH) AF: 0.0764 AC: 161 AN: 2108

Alfa AF: 0.0529 Hom.: 26

Bravo AF: 0.0564

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.36
DANN	Benign	0.37
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10516528; hg19: chr4-106739593;