4-105710713-A-G

Variant names:

• chr4-105710713-A-G
• rs11727735
• NM_001370181.1:c.-22+1697A>G

Variant summary

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

The NM_001370181.1(GSTCD):​c.-22+1697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,220 control chromosomes in the GnomAD database, including 208 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 (208 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTCD NM_001370181.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTCD	NM_001370181.1	c.-22+1697A>G		intron_variant	Intron 1 of 11	ENST00000515279.6	NP_001357110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTCD	ENST00000515279.6	c.-22+1697A>G		intron_variant	Intron 1 of 11	5	NM_001370181.1	ENSP00000422354.1

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6801 AN: 152102 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0640

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0678

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0446 AC: 6796 AN: 152220 Hom.: 208 Cov.: 32 AF XY: 0.0422 AC XY: 3140 AN XY: 74418

African (AFR) AF: 0.0115 AC: 479 AN: 41522

American (AMR) AF: 0.0638 AC: 976 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0211 AC: 102 AN: 4832

European-Finnish (FIN) AF: 0.0317 AC: 336 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0639 AC: 4348 AN: 68004

Other (OTH) AF: 0.0676 AC: 143 AN: 2116

Alfa AF: 0.0594 Hom.: 632

Bravo AF: 0.0465

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		-0.29
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism

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: rs11727735; hg19: chr4-106631870;