NM_004638.4:c.759+88A>G

Variant names:

• chr6-31625699-A-G
• rs2260000
• NM_004638.4:c.759+88A>G

Variant summary

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

The NM_004638.4(PRRC2A):​c.759+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,582,172 control chromosomes in the GnomAD database, including 112,291 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 0.30 (8621 hom., cov: 31)
  • Exomes 𝑓: 0.37 (103670 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• Publications: 56 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]

ENSG00000289282 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.572 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	NM_004638.4	MANE Select	c.759+88A>G		intron	N/A	NP_004629.3
	PRRC2A	NM_080686.3		c.759+88A>G		intron	N/A	NP_542417.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.759+88A>G		intron	N/A	ENSP00000365201.2
	PRRC2A	ENST00000376007.8	TSL:1	c.759+88A>G		intron	N/A	ENSP00000365175.4
	PRRC2A	ENST00000469577.5	TSL:5	n.604+88A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45602 AN: 151958 Hom.: 8613 Cov.: 31

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.371 AC: 530115 AN: 1430096 Hom.: 103670 Cov.: 32 AF XY: 0.379 AC XY: 270129 AN XY: 713132

African (AFR) AF: 0.0701 AC: 2295 AN: 32758

American (AMR) AF: 0.409 AC: 18239 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 14160 AN: 25888

East Asian (EAS) AF: 0.568 AC: 22449 AN: 39500

South Asian (SAS) AF: 0.521 AC: 44565 AN: 85512

European-Finnish (FIN) AF: 0.317 AC: 16928 AN: 53376

Middle Eastern (MID) AF: 0.455 AC: 2602 AN: 5718

European-Non Finnish (NFE) AF: 0.357 AC: 386669 AN: 1083402

Other (OTH) AF: 0.374 AC: 22208 AN: 59358

GnomAD4 genome AF: 0.300 AC: 45621 AN: 152076 Hom.: 8621 Cov.: 31 AF XY: 0.305 AC XY: 22679 AN XY: 74334

African (AFR) AF: 0.0798 AC: 3311 AN: 41502

American (AMR) AF: 0.347 AC: 5313 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1896 AN: 3464

East Asian (EAS) AF: 0.590 AC: 3043 AN: 5158

South Asian (SAS) AF: 0.528 AC: 2546 AN: 4818

European-Finnish (FIN) AF: 0.315 AC: 3337 AN: 10578

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24872 AN: 67944

Other (OTH) AF: 0.335 AC: 706 AN: 2110

Alfa AF: 0.347 Hom.: 28721

Bravo AF: 0.289

Asia WGS AF: 0.540 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.44
PhyloP100		-0.83
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: rs2260000; hg19: chr6-31593476;