4-105776097-G-A

Variant names:

• chr4-105776097-G-A
• rs11735851
• NM_001370181.1:c.1240+46598G>A

Variant summary

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

The NM_001370181.1(GSTCD):​c.1240+46598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 152,284 control chromosomes in the GnomAD database, including 212 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 0.045 (212 hom., cov: 32)
• Consequence: GSTCD NM_001370181.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798
• Publications: 5 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370181.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTCD	NM_001370181.1	MANE Select	c.1240+46598G>A		intron	N/A	NP_001357110.1
	GSTCD	NM_001031720.3		c.1240+46598G>A		intron	N/A	NP_001026890.2
	GSTCD	NM_024751.3		c.979+46598G>A		intron	N/A	NP_079027.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTCD	ENST00000515279.6	TSL:5 MANE Select	c.1240+46598G>A		intron	N/A	ENSP00000422354.1
	GSTCD	ENST00000360505.9	TSL:1	c.1240+46598G>A		intron	N/A	ENSP00000353695.5
	GSTCD	ENST00000394728.4	TSL:5	c.1240+46598G>A		intron	N/A	ENSP00000378216.3

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6831 AN: 152166 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0638

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0216

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0643

Gnomad OTH AF: 0.0672

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

GnomAD4 genome AF: 0.0448 AC: 6826 AN: 152284 Hom.: 212 Cov.: 32 AF XY: 0.0424 AC XY: 3156 AN XY: 74468

African (AFR) AF: 0.0116 AC: 484 AN: 41572

American (AMR) AF: 0.0636 AC: 973 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0216 AC: 104 AN: 4820

European-Finnish (FIN) AF: 0.0317 AC: 336 AN: 10612

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0643 AC: 4376 AN: 68018

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.0474 Hom.: 24

Bravo AF: 0.0466

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-0.80
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: rs11735851; hg19: chr4-106697254;