rs3735461

chr7-7640013-A-G

Variant summary

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

The NM_002947.5(RPA3):c.99+307T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 371,524 control chromosomes in the GnomAD database, including 30,993 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 0.34 (10947 hom., cov: 32)
  • Exomes 𝑓: 0.41 (20046 hom.)
• Consequence: RPA3 NM_002947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

Genes affected

RPA3 (HGNC:10291): (replication protein A3) Enables damaged DNA binding activity and single-stranded DNA binding activity. Involved in DNA repair and DNA replication. Part of DNA replication factor A complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPA3	NM_002947.5	c.99+307T>C		intron_variant		ENST00000223129.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPA3	ENST00000223129.8	c.99+307T>C		intron_variant		1	NM_002947.5	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51858 AN: 152006 Hom.: 10945 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.409 AC: 89840 AN: 219400 Hom.: 20046 Cov.: 0 AF XY: 0.399 AC XY: 46421 AN XY: 116198

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.0922

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.341 AC: 51851 AN: 152124 Hom.: 10947 Cov.: 32 AF XY: 0.340 AC XY: 25280 AN XY: 74336

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.346

Alfa AF: 0.417 Hom.: 7655

Bravo AF: 0.326

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.6
Dann	Benign	0.59

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: rs3735461; hg19: chr7-7679644;