rs3115663

chr6-31634066-T-C

Variant summary

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

The NM_004638.4(PRRC2A):c.4719+77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,579,806 control chromosomes in the GnomAD database, including 26,347 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 0.17 (2374 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23973 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

PRRC2A (HGNC:13918): (proline rich coiled-coil 2A) A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRC2A	NM_004638.4	c.4719+77T>C		intron_variant		ENST00000376033.3
PRRC2A	NM_080686.3	c.4719+77T>C		intron_variant
PRRC2A	XM_047419336.1	c.4719+77T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRC2A	ENST00000376033.3	c.4719+77T>C		intron_variant		1	NM_004638.4	P1
PRRC2A	ENST00000376007.8	c.4719+77T>C		intron_variant		1		P1
PRRC2A	ENST00000460302.1	n.113T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25671 AN: 152064 Hom.: 2374 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0786

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.177 AC: 253153 AN: 1427624 Hom.: 23973 Cov.: 34 AF XY: 0.175 AC XY: 124191 AN XY: 710462

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.0835

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0463

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.169 AC: 25671 AN: 152182 Hom.: 2374 Cov.: 32 AF XY: 0.164 AC XY: 12223 AN XY: 74412

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0984

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0792

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.147

Alfa AF: 0.177 Hom.: 3992

Bravo AF: 0.166

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.14
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3115663; hg19: chr6-31601843;