19-12951169-C-T

Variant names:

• chr19-12951169-C-T
• rs2974754
• NM_005053.4:c.814-1520C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAD23A	NM_005053.4	c.814-1520C>T		intron_variant	Intron 7 of 8	ENST00000586534.6	NP_005044.1
RAD23A	NM_001270362.2	c.811-1520C>T		intron_variant	Intron 7 of 8		NP_001257291.1
RAD23A	NM_001270363.2	c.813+1761C>T		intron_variant	Intron 7 of 7		NP_001257292.1
RAD23A	NR_072976.2	n.845-1520C>T		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD23A	ENST00000586534.6	c.814-1520C>T		intron_variant	Intron 7 of 8	1	NM_005053.4	ENSP00000467024.1

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

African (AFR) AF: 0.0788 AC: 3274 AN: 41536

American (AMR) AF: 0.270 AC: 4116 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1594 AN: 3468

East Asian (EAS) AF: 0.181 AC: 938 AN: 5180

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4822

European-Finnish (FIN) AF: 0.474 AC: 5005 AN: 10566

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27949 AN: 67960

Other (OTH) AF: 0.330 AC: 698 AN: 2114

Alfa AF: 0.386 Hom.: 18018

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
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2974754; hg19: chr19-13061983;