chr4-105845339-A-T

Variant names:

• chr4-105845339-A-T
• rs11726124
• NM_001370181.1:c.1766-102A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370181.1(GSTCD):​c.1766-102A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000091 in 1,098,406 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: GSTCD NM_001370181.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTCD	NM_001370181.1	MANE Select	c.1766-102A>T		intron	N/A	NP_001357110.1	Q8NEC7-1
	GSTCD	NM_001031720.3		c.1766-102A>T		intron	N/A	NP_001026890.2	Q8NEC7-1
	GSTCD	NM_024751.3		c.1505-102A>T		intron	N/A	NP_079027.2	Q8NEC7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTCD	ENST00000515279.6	TSL:5 MANE Select	c.1766-102A>T		intron	N/A	ENSP00000422354.1	Q8NEC7-1
	GSTCD	ENST00000360505.9	TSL:1	c.1766-102A>T		intron	N/A	ENSP00000353695.5	Q8NEC7-1
	GSTCD	ENST00000394728.4	TSL:5	c.1766-102A>T		intron	N/A	ENSP00000378216.3	Q8NEC7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.10e-7 AC: 1 AN: 1098406 Hom.: 0 AF XY: 0.00000180 AC XY: 1 AN XY: 554826

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26516

American (AMR) AF: 0.00 AC: 0 AN: 41532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21462

East Asian (EAS) AF: 0.00 AC: 0 AN: 37686

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 71082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4972

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 799780

Other (OTH) AF: 0.00 AC: 0 AN: 48132

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.97
DANN	Benign	0.68
PhyloP100		0.22

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: rs11726124; hg19: chr4-106766496;