rs3816804

Variant names:

• chr12-56286961-C-T
• rs3816804
• NM_004077.3:c.43-316G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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]

ENSG00000144785 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CS	NM_004077.3	c.43-316G>A		intron_variant	Intron 1 of 10	ENST00000351328.8	NP_004068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CS	ENST00000351328.8	c.43-316G>A		intron_variant	Intron 1 of 10	1	NM_004077.3	ENSP00000342056.3
ENSG00000144785	ENST00000549318.5	c.631-316G>A		intron_variant	Intron 7 of 8	5		ENSP00000446743.1

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

African (AFR) AF: 0.0149 AC: 618 AN: 41514

American (AMR) AF: 0.0576 AC: 881 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3468

East Asian (EAS) AF: 0.178 AC: 920 AN: 5180

South Asian (SAS) AF: 0.102 AC: 490 AN: 4816

European-Finnish (FIN) AF: 0.0989 AC: 1046 AN: 10580

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5916 AN: 68026

Other (OTH) AF: 0.0643 AC: 136 AN: 2114

Alfa AF: 0.0805 Hom.: 1743

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3816804; hg19: chr12-56680745;