12-56280982-G-A

Variant names:

• chr12-56280982-G-A
• rs773652
• NM_004077.3:c.588+1438C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004077.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CS	NM_004077.3	MANE Select	c.588+1438C>T		intron	N/A	NP_004068.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CS	ENST00000351328.8	TSL:1 MANE Select	c.588+1438C>T		intron	N/A	ENSP00000342056.3
	CS	ENST00000548567.5	TSL:1	c.390+1438C>T		intron	N/A	ENSP00000446779.1
	CS	ENST00000542324.6	TSL:2	c.549+1438C>T		intron	N/A	ENSP00000440543.2

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

African (AFR) AF: 0.472 AC: 19503 AN: 41352

American (AMR) AF: 0.882 AC: 13469 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3325 AN: 3472

East Asian (EAS) AF: 0.965 AC: 4995 AN: 5174

South Asian (SAS) AF: 0.979 AC: 4725 AN: 4826

European-Finnish (FIN) AF: 0.946 AC: 10032 AN: 10600

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63204 AN: 68028

Other (OTH) AF: 0.869 AC: 1836 AN: 2112

Alfa AF: 0.902 Hom.: 37179

Bravo AF: 0.786

Asia WGS AF: 0.894 AC: 3110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		-0.033
Mutation Taster		=100/0	polymorphism (auto)

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: rs773652; hg19: chr12-56674766;