rs7961855

chr12-121392140-C-T

Variant summary

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

The ENST00000557474.1(ENSG00000258435):n.179C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,974 control chromosomes in the GnomAD database, including 22,049 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 0.54 (22047 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: ENST00000557474.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

Genes affected

(HGNC:):

ANAPC5 (HGNC:15713): (anaphase promoting complex subunit 5) This gene encodes a tetratricopeptide repeat-containing component of the anaphase promoting complex/cyclosome (APC/C), a large E3 ubiquitin ligase that controls cell cycle progression by targeting a number of cell cycle regulators such as B-type cyclins for 26S proteasome-mediated degradation through ubiquitination. The encoded protein is required for the proper ubiquitination function of APC/C and for the interaction of APC/C with transcription coactivators. It also interacts with polyA binding protein and represses internal ribosome entry site-mediated translation. Multiple transcript variants encoding different isoforms have been found for this gene. These differences cause translation initiation at a downstream AUG and result in a shorter protein (isoform b), compared to isoform a. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903037	XR_007063498.1	n.563C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000557474.1	n.179C>T		non_coding_transcript_exon_variant	1/2	4
ANAPC5	ENST00000536837.1	c.-91+7471G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81226 AN: 151852 Hom.: 22015 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.535 AC: 81310 AN: 151970 Hom.: 22047 Cov.: 32 AF XY: 0.541 AC XY: 40159 AN XY: 74250

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.502

Alfa AF: 0.483 Hom.: 25098

Bravo AF: 0.528

Asia WGS AF: 0.574 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	12
Dann	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7961855; hg19: chr12-121829943;