rs3993757

Positions:

• chr6-31622969-C-T

Variant summary

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

The NM_004638.4(PRRC2A):​c.112+68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,297,820 control chromosomes in the GnomAD database, including 1,045 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 0.023 (160 hom., cov: 32)
  • Exomes 𝑓: 0.025 (885 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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]

PRRC2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.112+68C>T		intron_variant		ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.112+68C>T		intron_variant			NP_542417.2
PRRC2A	XM_047419336.1	c.112+68C>T		intron_variant			XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.112+68C>T		intron_variant		1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.112+68C>T		intron_variant		1		ENSP00000365175.4
PRRC2A	ENST00000469577.5	n.136-1292C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3509 AN: 152124 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0247 AC: 28284 AN: 1145578 Hom.: 885 Cov.: 16 AF XY: 0.0264 AC XY: 15448 AN XY: 585314

Gnomad4 AFR exome AF: 0.00353

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.0198

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.0658

Gnomad4 FIN exome AF: 0.0231

Gnomad4 NFE exome AF: 0.0169

Gnomad4 OTH exome AF: 0.0284

GnomAD4 genome AF: 0.0231 AC: 3511 AN: 152242 Hom.: 160 Cov.: 32 AF XY: 0.0249 AC XY: 1856 AN XY: 74434

Gnomad4 AFR AF: 0.00402

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.0662

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0187 Hom.: 12

Bravo AF: 0.0209

Asia WGS AF: 0.101 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.46
DANN	Benign	0.75

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: rs3993757; hg19: chr6-31590746;