chr7-7640013-A-G

Variant names:

• chr7-7640013-A-G
• rs3735461
• NM_002947.5:c.99+307T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002947.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPA3	NM_002947.5	MANE Select	c.99+307T>C		intron	N/A	NP_002938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPA3	ENST00000223129.8	TSL:1 MANE Select	c.99+307T>C		intron	N/A	ENSP00000223129.4
	RPA3	ENST00000401447.1	TSL:3	c.-127T>C		5_prime_UTR	Exon 1 of 4	ENSP00000385383.1
	RPA3	ENST00000396682.6	TSL:3	c.99+307T>C		intron	N/A	ENSP00000379914.2

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

African (AFR) AF: 0.104 AC: 549 AN: 5286

American (AMR) AF: 0.407 AC: 2511 AN: 6168

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 2743 AN: 7016

East Asian (EAS) AF: 0.0922 AC: 894 AN: 9698

South Asian (SAS) AF: 0.298 AC: 8897 AN: 29884

European-Finnish (FIN) AF: 0.478 AC: 6155 AN: 12874

Middle Eastern (MID) AF: 0.380 AC: 394 AN: 1036

European-Non Finnish (NFE) AF: 0.465 AC: 62534 AN: 134496

Other (OTH) AF: 0.399 AC: 5163 AN: 12942

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

African (AFR) AF: 0.100 AC: 4162 AN: 41544

American (AMR) AF: 0.414 AC: 6322 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3466

East Asian (EAS) AF: 0.112 AC: 578 AN: 5170

South Asian (SAS) AF: 0.272 AC: 1313 AN: 4822

European-Finnish (FIN) AF: 0.484 AC: 5105 AN: 10556

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31784 AN: 67968

Other (OTH) AF: 0.346 AC: 729 AN: 2108

Alfa AF: 0.408 Hom.: 10498

Bravo AF: 0.326

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.59
PhyloP100		0.024
PromoterAI		-0.021	Neutral
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: rs3735461; hg19: chr7-7679644;