rs1046089

Variant names:

• chr6-31635190-G-A
• rs1046089
• NM_004638.4:c.5219G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004638.4(PRRC2A):​c.5219G>A​(p.Arg1740His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,613,872 control chromosomes in the GnomAD database, including 106,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (12571 hom., cov: 32)
  • Exomes 𝑓: 0.35 (93991 hom.)
• Consequence: PRRC2A NM_004638.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.41
• Publications: 123 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.2975626E-4).
• BP6: Variant 6-31635190-G-A is Benign according to our data. Variant chr6-31635190-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060262.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 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.5219G>A	p.Arg1740His	missense	Exon 22 of 31	NP_004629.3
	PRRC2A	NM_080686.3		c.5219G>A	p.Arg1740His	missense	Exon 22 of 31	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.5219G>A	p.Arg1740His	missense	Exon 22 of 31	ENSP00000365201.2	P48634-1
	PRRC2A	ENST00000376007.8	TSL:1	c.5219G>A	p.Arg1740His	missense	Exon 22 of 31	ENSP00000365175.4	P48634-1
	PRRC2A	ENST00000484787.1	TSL:2	n.630G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60663 AN: 151920 Hom.: 12565 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.357 AC: 89663 AN: 251378 AF XY: 0.346

Gnomad AFR exome AF: 0.513

Gnomad AMR exome AF: 0.383

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.385

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.354 AC: 517868 AN: 1461834 Hom.: 93991 Cov.: 68 AF XY: 0.349 AC XY: 253786 AN XY: 727212

African (AFR) AF: 0.514 AC: 17198 AN: 33476

American (AMR) AF: 0.380 AC: 16985 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 5276 AN: 26134

East Asian (EAS) AF: 0.369 AC: 14645 AN: 39700

South Asian (SAS) AF: 0.272 AC: 23443 AN: 86252

European-Finnish (FIN) AF: 0.476 AC: 25442 AN: 53420

Middle Eastern (MID) AF: 0.288 AC: 1661 AN: 5766

European-Non Finnish (NFE) AF: 0.353 AC: 392135 AN: 1111974

Other (OTH) AF: 0.349 AC: 21083 AN: 60392

GnomAD4 genome AF: 0.399 AC: 60700 AN: 152038 Hom.: 12571 Cov.: 32 AF XY: 0.402 AC XY: 29892 AN XY: 74310

African (AFR) AF: 0.503 AC: 20848 AN: 41476

American (AMR) AF: 0.367 AC: 5607 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1884 AN: 5150

South Asian (SAS) AF: 0.293 AC: 1411 AN: 4818

European-Finnish (FIN) AF: 0.499 AC: 5263 AN: 10556

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23849 AN: 67966

Other (OTH) AF: 0.359 AC: 760 AN: 2116

Alfa AF: 0.364 Hom.: 46320

Bravo AF: 0.397

TwinsUK AF: 0.351 AC: 1300

ALSPAC AF: 0.348 AC: 1343

ESP6500AA AF: 0.510 AC: 2245

ESP6500EA AF: 0.345 AC: 2971

ExAC AF: 0.357 AC: 43360

Asia WGS AF: 0.339 AC: 1178 AN: 3478

EpiCase AF: 0.324

EpiControl AF: 0.318

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PRRC2A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.00083	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Benign	0.053	T
Sift4G	Uncertain	0.029	D
Polyphen		0.96	D
Vest4		0.19
MPC		0.20
ClinPred		0.012	T
GERP RS		5.5
Varity_R		0.13
gMVP		0.35
Mutation Taster		=97/3	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: rs1046089; hg19: chr6-31602967; COSMIC: COSV52990077; COSMIC: COSV52990077;