6-31627710-A-G

Variant names:

• chr6-31627710-A-G
• rs2736171
• NM_004638.4:c.1291-55A>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.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
• Publications: 39 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 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.1291-55A>G		intron	N/A	NP_004629.3
	PRRC2A	NM_080686.3		c.1291-55A>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.1291-55A>G		intron	N/A	ENSP00000365201.2
	PRRC2A	ENST00000376007.8	TSL:1	c.1291-55A>G		intron	N/A	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

African (AFR) AF: 0.186 AC: 6023 AN: 32324

American (AMR) AF: 0.467 AC: 18963 AN: 40640

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 17013 AN: 24738

East Asian (EAS) AF: 0.587 AC: 22903 AN: 39016

South Asian (SAS) AF: 0.539 AC: 45081 AN: 83708

European-Finnish (FIN) AF: 0.320 AC: 16253 AN: 50812

Middle Eastern (MID) AF: 0.554 AC: 2376 AN: 4288

European-Non Finnish (NFE) AF: 0.375 AC: 409946 AN: 1092922

Other (OTH) AF: 0.412 AC: 24232 AN: 58772

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

African (AFR) AF: 0.196 AC: 8148 AN: 41474

American (AMR) AF: 0.408 AC: 6219 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2386 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2949 AN: 5168

South Asian (SAS) AF: 0.545 AC: 2623 AN: 4816

European-Finnish (FIN) AF: 0.318 AC: 3367 AN: 10574

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26389 AN: 67960

Other (OTH) AF: 0.410 AC: 864 AN: 2108

Alfa AF: 0.385 Hom.: 32403

Bravo AF: 0.348

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.66
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2736171; hg19: chr6-31595487; COSMIC: COSV63224277; COSMIC: COSV63224277;