6-159778655-T-C

Variant names:

• chr6-159778655-T-C
• rs15982
• NM_030752.3:c.*390A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005891.3(ACAT2):​c.1024-4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,612,640 control chromosomes in the GnomAD database, including 458,906 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.70 (38340 hom., cov: 31)
  • Exomes 𝑓: 0.76 (420566 hom.)
• Consequence: ACAT2 NM_005891.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006833
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-159778655-T-C is Benign according to our data. Variant chr6-159778655-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCP1	NM_030752.3	c.*390A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000321394.12	NP_110379.2
ACAT2	NM_005891.3	c.1024-4T>C		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000367048.5	NP_005882.2
TCP1	NM_001008897.2	c.*390A>G		3_prime_UTR_variant	Exon 11 of 11		NP_001008897.1
ACAT2	NM_001303253.1	c.1111-4T>C		splice_region_variant, intron_variant	Intron 8 of 8		NP_001290182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCP1	ENST00000321394	c.*390A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_030752.3	ENSP00000317334.7
ACAT2	ENST00000367048.5	c.1024-4T>C		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_005891.3	ENSP00000356015.4
ACAT2	ENST00000472052.1	n.1254-4T>C		splice_region_variant, intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106631 AN: 151898 Hom.: 38334 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.709

GnomAD3 exomes AF: 0.746 AC: 186772 AN: 250410 Hom.: 70558 AF XY: 0.748 AC XY: 101153 AN XY: 135268

Gnomad AFR exome AF: 0.548

Gnomad AMR exome AF: 0.823

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.578

Gnomad SAS exome AF: 0.770

Gnomad FIN exome AF: 0.822

Gnomad NFE exome AF: 0.763

Gnomad OTH exome AF: 0.751

GnomAD4 exome AF: 0.757 AC: 1105470 AN: 1460624 Hom.: 420566 Cov.: 41 AF XY: 0.757 AC XY: 549931 AN XY: 726636

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.677

Gnomad4 EAS exome AF: 0.564

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 0.727

GnomAD4 genome AF: 0.702 AC: 106672 AN: 152016 Hom.: 38340 Cov.: 31 AF XY: 0.706 AC XY: 52456 AN XY: 74276

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.703

Alfa AF: 0.741 Hom.: 57292

Bravo AF: 0.688

Asia WGS AF: 0.662 AC: 2299 AN: 3478

EpiCase AF: 0.750

EpiControl AF: 0.759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.0
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000068
dbscSNV1_RF	Benign	0.0020
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: rs15982; hg19: chr6-160199687; COSMIC: COSV58458980; COSMIC: COSV58458980;