rs773652

Positions:

• chr12-56280982-G-A
• chr12-56280982-G-C

Variant summary

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

The NM_004077.3(CS):​c.588+1438C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,038 control chromosomes in the GnomAD database, including 52,401 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 0.80 (52401 hom., cov: 31)
• Consequence: CS NM_004077.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

Genes affected

CS (HGNC:2422): (citrate synthase) The protein encoded by this gene is a Krebs tricarboxylic acid cycle enzyme that catalyzes the synthesis of citrate from oxaloacetate and acetyl coenzyme A. The enzyme is found in nearly all cells capable of oxidative metablism. This protein is nuclear encoded and transported into the mitochondrial matrix, where the mature form is found. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CS	NM_004077.3	c.588+1438C>T		intron_variant		ENST00000351328.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CS	ENST00000351328.8	c.588+1438C>T		intron_variant		1	NM_004077.3	P1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122212 AN: 151920 Hom.: 52405 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.804 AC: 122234 AN: 152038 Hom.: 52401 Cov.: 31 AF XY: 0.810 AC XY: 60230 AN XY: 74328

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.958

Gnomad4 EAS AF: 0.965

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.946

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.869

Alfa AF: 0.905 Hom.: 33831

Bravo AF: 0.786

Asia WGS AF: 0.894 AC: 3110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.36

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: rs773652; hg19: chr12-56674766;