rs11728716

Positions:

• chr4-105834839-G-A
• chr4-105834839-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370181.1(GSTCD):​c.1664+245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 152,262 control chromosomes in the GnomAD database, including 213 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 0.046 (213 hom., cov: 32)
• Consequence: GSTCD NM_001370181.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTCD	NM_001370181.1	c.1664+245G>A		intron_variant		ENST00000515279.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTCD	ENST00000515279.6	c.1664+245G>A		intron_variant		5	NM_001370181.1	P1

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6945 AN: 152144 Hom.: 214 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0456 AC: 6940 AN: 152262 Hom.: 213 Cov.: 32 AF XY: 0.0432 AC XY: 3215 AN XY: 74454

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0631

Gnomad4 ASJ AF: 0.0720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0660

Gnomad4 OTH AF: 0.0686

Alfa AF: 0.0306 Hom.: 23

Bravo AF: 0.0474

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs11728716; hg19: chr4-106755996;