rs2736157

Variant names:

• chr6-31633043-A-G
• rs2736157
• NM_004638.4:c.4319+51A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-31633043-A-G
• chr6-31633043-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004638.4(PRRC2A):​c.4319+51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,450,738 control chromosomes in the GnomAD database, including 24,793 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 (2379 hom., cov: 32)
  • Exomes 𝑓: 0.18 (22414 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004638.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	NM_004638.4	MANE Select	c.4319+51A>G		intron	N/A	NP_004629.3
	PRRC2A	NM_080686.3		c.4319+51A>G		intron	N/A	NP_542417.2	A0A1U9X974

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.4319+51A>G		intron	N/A	ENSP00000365201.2	P48634-1
	PRRC2A	ENST00000376007.8	TSL:1	c.4319+51A>G		intron	N/A	ENSP00000365175.4	P48634-1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25664 AN: 151982 Hom.: 2379 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0788

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

GnomAD2 exomes AF: 0.146 AC: 11244 AN: 76768 AF XY: 0.149

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.0857

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.0965

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.180 AC: 234154 AN: 1298638 Hom.: 22414 Cov.: 32 AF XY: 0.178 AC XY: 112494 AN XY: 631260

African (AFR) AF: 0.210 AC: 6001 AN: 28638

American (AMR) AF: 0.0879 AC: 1925 AN: 21902

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2374 AN: 19404

East Asian (EAS) AF: 0.0409 AC: 1430 AN: 34984

South Asian (SAS) AF: 0.118 AC: 7735 AN: 65552

European-Finnish (FIN) AF: 0.162 AC: 5555 AN: 34342

Middle Eastern (MID) AF: 0.0916 AC: 460 AN: 5020

European-Non Finnish (NFE) AF: 0.193 AC: 199635 AN: 1034772

Other (OTH) AF: 0.167 AC: 9039 AN: 54024

GnomAD4 genome AF: 0.169 AC: 25664 AN: 152100 Hom.: 2379 Cov.: 32 AF XY: 0.164 AC XY: 12218 AN XY: 74360

African (AFR) AF: 0.193 AC: 8005 AN: 41476

American (AMR) AF: 0.0983 AC: 1504 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3470

East Asian (EAS) AF: 0.0794 AC: 411 AN: 5178

South Asian (SAS) AF: 0.124 AC: 601 AN: 4830

European-Finnish (FIN) AF: 0.162 AC: 1711 AN: 10578

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12511 AN: 67958

Other (OTH) AF: 0.148 AC: 313 AN: 2110

Alfa AF: 0.183 Hom.: 7139

Bravo AF: 0.166

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.32
PhyloP100		-3.1
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.1
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: rs2736157; hg19: chr6-31600820;