rs4832

chr6-159778994-A-C

Variant summary

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

The NM_030752.3(TCP1):c.*51T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,581,040 control chromosomes in the GnomAD database, including 33,207 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 0.20 (3188 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30019 hom.)
• Consequence: TCP1 NM_030752.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

Genes affected

ACAT2 (HGNC:94): (acetyl-CoA acetyltransferase 2) The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase. This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

TCP1 (HGNC:11655): (t-complex 1) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized. In addition, three pseudogenes that appear to be derived from this gene have been found. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAT2	NM_005891.3	c.*165A>C		3_prime_UTR_variant	9/9	ENST00000367048.5
TCP1	NM_030752.3	c.*51T>G		3_prime_UTR_variant	12/12	ENST00000321394.12
TCP1	NM_001008897.2	c.*51T>G		3_prime_UTR_variant	11/11
ACAT2	NM_001303253.1	c.*165A>C		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCP1	ENST00000321394.12	c.*51T>G		3_prime_UTR_variant	12/12	1	NM_030752.3	P1
ACAT2	ENST00000367048.5	c.*165A>C		3_prime_UTR_variant	9/9	1	NM_005891.3	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30337 AN: 152106 Hom.: 3187 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.213 AC: 50263 AN: 235820 Hom.: 5933 AF XY: 0.216 AC XY: 27565 AN XY: 127678

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.396

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.200 AC: 286326 AN: 1428816 Hom.: 30019 Cov.: 28 AF XY: 0.203 AC XY: 144031 AN XY: 709116

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.199 AC: 30348 AN: 152224 Hom.: 3188 Cov.: 32 AF XY: 0.206 AC XY: 15302 AN XY: 74422

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.209

Alfa AF: 0.181 Hom.: 2673

Bravo AF: 0.193

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.1
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4832; hg19: chr6-160200026; COSMIC: COSV58458988; COSMIC: COSV58458988;