19-12951169-C-T

Position:

• chr19-12951169-C-T

Variant summary

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

The NM_005053.4(RAD23A):​c.814-1520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,116 control chromosomes in the GnomAD database, including 8,589 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 0.30 (8589 hom., cov: 32)
• Consequence: RAD23A NM_005053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

Genes affected

RAD23A (HGNC:9812): (RAD23 homolog A, nucleotide excision repair protein) The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in nucleotide excision repair. Proteins in this family have a modular domain structure consisting of an ubiquitin-like domain (UbL), ubiquitin-associated domain 1 (UbA1), XPC-binding domain and UbA2. The protein encoded by this gene plays an important role in nucleotide excision repair and also in delivery of polyubiquitinated proteins to the proteasome. Alternative splicing results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD23A	NM_005053.4	c.814-1520C>T		intron_variant		ENST00000586534.6	NP_005044.1
RAD23A	NM_001270362.2	c.811-1520C>T		intron_variant			NP_001257291.1
RAD23A	NM_001270363.2	c.813+1761C>T		intron_variant			NP_001257292.1
RAD23A	NR_072976.2	n.845-1520C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD23A	ENST00000586534.6	c.814-1520C>T		intron_variant		1	NM_005053.4	ENSP00000467024	A1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45402 AN: 151998 Hom.: 8586 Cov.: 32

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45391 AN: 152116 Hom.: 8589 Cov.: 32 AF XY: 0.298 AC XY: 22150 AN XY: 74346

Gnomad4 AFR AF: 0.0788

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.330

Alfa AF: 0.395 Hom.: 14043

Bravo AF: 0.277

Asia WGS AF: 0.179 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.40

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: rs2974754; hg19: chr19-13061983;