6-31627710-A-G

Position:

• chr6-31627710-A-G

Variant summary

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

The NM_004638.4(PRRC2A):​c.1291-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,579,246 control chromosomes in the GnomAD database, including 126,818 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 0.35 (10563 hom., cov: 32)
  • Exomes 𝑓: 0.39 (116255 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.1291-55A>G		intron_variant		ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.1291-55A>G		intron_variant			NP_542417.2
PRRC2A	XM_047419336.1	c.1291-55A>G		intron_variant			XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.1291-55A>G		intron_variant		1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.1291-55A>G		intron_variant		1		ENSP00000365175.4

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53504 AN: 151908 Hom.: 10546 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.394 AC: 562790 AN: 1427220 Hom.: 116255 AF XY: 0.402 AC XY: 283828 AN XY: 706692

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.688

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.352 AC: 53560 AN: 152026 Hom.: 10563 Cov.: 32 AF XY: 0.355 AC XY: 26412 AN XY: 74326

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.410

Alfa AF: 0.405 Hom.: 19669

Bravo AF: 0.348

Asia WGS AF: 0.565 AC: 1964 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	0.19
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2736171; hg19: chr6-31595487; COSMIC: COSV63224277; COSMIC: COSV63224277;