NM_004638.4:c.290+122A>G

Variant names:

• chr6-31624031-A-G
• rs3130070
• NM_004638.4:c.290+122A>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.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
• Publications: 33 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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.290+122A>G		intron	N/A	NP_004629.3
	PRRC2A	NM_080686.3		c.290+122A>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.290+122A>G		intron	N/A	ENSP00000365201.2	P48634-1
	PRRC2A	ENST00000376007.8	TSL:1	c.290+122A>G		intron	N/A	ENSP00000365175.4	P48634-1
	ENSG00000289282	ENST00000687518.1		c.36+122A>G		intron	N/A	ENSP00000509222.1	A0A8I5QKQ9

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

African (AFR) AF: 0.203 AC: 4979 AN: 24484

American (AMR) AF: 0.0857 AC: 1952 AN: 22766

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 2169 AN: 18172

East Asian (EAS) AF: 0.0414 AC: 1463 AN: 35296

South Asian (SAS) AF: 0.116 AC: 7225 AN: 62504

European-Finnish (FIN) AF: 0.160 AC: 7126 AN: 44662

Middle Eastern (MID) AF: 0.0909 AC: 400 AN: 4400

European-Non Finnish (NFE) AF: 0.189 AC: 158068 AN: 837074

Other (OTH) AF: 0.163 AC: 7725 AN: 47370

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

African (AFR) AF: 0.193 AC: 8017 AN: 41466

American (AMR) AF: 0.0986 AC: 1508 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3470

East Asian (EAS) AF: 0.0786 AC: 407 AN: 5180

South Asian (SAS) AF: 0.124 AC: 601 AN: 4828

European-Finnish (FIN) AF: 0.162 AC: 1712 AN: 10596

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

European-Non Finnish (NFE) AF: 0.184 AC: 12528 AN: 68006

Other (OTH) AF: 0.149 AC: 314 AN: 2114

Alfa AF: 0.181 Hom.: 9831

Bravo AF: 0.166

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.061
DANN	Benign	0.29
PhyloP100		-1.5
PromoterAI		0.012	Neutral
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: rs3130070; hg19: chr6-31591808;