6-31624031-A-G

Variant names:

• chr6-31624031-A-G
• rs3130070
• NM_004638.4:c.290+122A>G

Variant summary

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

The NM_004638.4(PRRC2A):​c.290+122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,248,878 control chromosomes in the GnomAD database, including 20,628 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 (2378 hom., cov: 32)
  • Exomes 𝑓: 0.17 (18250 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

ENSG00000289282 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.290+122A>G		intron_variant	Intron 3 of 30	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.290+122A>G		intron_variant	Intron 3 of 30		NP_542417.2
PRRC2A	XM_047419336.1	c.290+122A>G		intron_variant	Intron 3 of 29		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.290+122A>G		intron_variant	Intron 3 of 30	1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.290+122A>G		intron_variant	Intron 3 of 30	1		ENSP00000365175.4
ENSG00000289282	ENST00000687518.1	c.36+122A>G		intron_variant	Intron 1 of 4			ENSP00000509222.1
PRRC2A	ENST00000469577.5	n.136-230A>G		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25691 AN: 152032 Hom.: 2378 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0780

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.174 AC: 191107 AN: 1096728 Hom.: 18250 AF XY: 0.172 AC XY: 93542 AN XY: 543688

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.0857

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0414

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.169 AC: 25691 AN: 152150 Hom.: 2378 Cov.: 32 AF XY: 0.164 AC XY: 12228 AN XY: 74394

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0786

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.149

Alfa AF: 0.178 Hom.: 3410

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	-0.85
CADD	Benign	0.061
DANN	Benign	0.29

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: rs3130070; hg19: chr6-31591808;