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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

33 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRRC2ANM_004638.4 linkc.290+122A>G intron_variant Intron 3 of 30 ENST00000376033.3 NP_004629.3 P48634-1A0A1U9X974
PRRC2ANM_080686.3 linkc.290+122A>G intron_variant Intron 3 of 30 NP_542417.2 P48634-1A0A1U9X974
PRRC2AXM_047419336.1 linkc.290+122A>G intron_variant Intron 3 of 29 XP_047275292.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRRC2AENST00000376033.3 linkc.290+122A>G intron_variant Intron 3 of 30 1 NM_004638.4 ENSP00000365201.2 P48634-1
PRRC2AENST00000376007.8 linkc.290+122A>G intron_variant Intron 3 of 30 1 ENSP00000365175.4 P48634-1
ENSG00000289282ENST00000687518.1 linkc.36+122A>G intron_variant Intron 1 of 4 ENSP00000509222.1 A0A8I5QKQ9
PRRC2AENST00000469577.5 linkn.136-230A>G intron_variant Intron 1 of 7 5

Frequencies

GnomAD3 genomes
AF:
0.169
AC:
25691
AN:
152032
Hom.:
2378
Cov.:
32
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
8128
16256
24383
32511
40639
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
5266
10532
15798
21064
26330
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.169
AC:
25691
AN:
152150
Hom.:
2378
Cov.:
32
AF XY:
0.164
AC XY:
12228
AN XY:
74394
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1115
2229
3344
4458
5573
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
274
548
822
1096
1370
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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 v4.3

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

Publications

Other links and lift over

dbSNP: rs3130070; hg19: chr6-31591808; API