rs3816804

chr12-56286961-C-T

Variant summary

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

The NM_004077.3(CS):c.43-316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 152,184 control chromosomes in the GnomAD database, including 450 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 0.069 (450 hom., cov: 31)
• Consequence: CS NM_004077.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CS	NM_004077.3	c.43-316G>A		intron_variant		ENST00000351328.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CS	ENST00000351328.8	c.43-316G>A		intron_variant		1	NM_004077.3	P1

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10514 AN: 152066 Hom.: 450 Cov.: 31

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.0636

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

GnomAD4 genome AF: 0.0690 AC: 10506 AN: 152184 Hom.: 450 Cov.: 31 AF XY: 0.0708 AC XY: 5264 AN XY: 74398

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.0576

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0989

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0812 Hom.: 553

Bravo AF: 0.0627

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.48
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3816804; hg19: chr12-56680745;