chr16-14436869-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002582.4(PARN):​c.1865-97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 864,516 control chromosomes in the GnomAD database, including 18,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2652 hom., cov: 32)
Exomes 𝑓: 0.20 ( 16043 hom. )

Consequence

PARN
NM_002582.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.80

Publications

2 publications found
Variant links:
Genes affected
PARN (HGNC:8609): (poly(A)-specific ribonuclease) The protein encoded by this gene is a 3'-exoribonuclease, with similarity to the RNase D family of 3'-exonucleases. It prefers poly(A) as the substrate, hence, efficiently degrades poly(A) tails of mRNAs. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs. This protein is also involved in silencing of certain maternal mRNAs during oocyte maturation and early embryonic development, as well as in nonsense-mediated decay (NMD) of mRNAs that contain premature stop codons. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
PARN Gene-Disease associations (from GenCC):
  • dyskeratosis congenita, autosomal recessive 6
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
  • pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • dyskeratosis congenita
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Hoyeraal-Hreidarsson syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 16-14436869-G-A is Benign according to our data. Variant chr16-14436869-G-A is described in ClinVar as [Benign]. Clinvar id is 1178066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PARNNM_002582.4 linkc.1865-97C>T intron_variant Intron 23 of 23 ENST00000437198.7 NP_002573.1 O95453-1B3KN69

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PARNENST00000437198.7 linkc.1865-97C>T intron_variant Intron 23 of 23 1 NM_002582.4 ENSP00000387911.2 O95453-1

Frequencies

GnomAD3 genomes
AF:
0.168
AC:
25590
AN:
152108
Hom.:
2654
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0544
Gnomad AMI
AF:
0.173
Gnomad AMR
AF:
0.159
Gnomad ASJ
AF:
0.310
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.129
Gnomad FIN
AF:
0.271
Gnomad MID
AF:
0.282
Gnomad NFE
AF:
0.230
Gnomad OTH
AF:
0.203
GnomAD4 exome
AF:
0.201
AC:
143184
AN:
712292
Hom.:
16043
AF XY:
0.199
AC XY:
74511
AN XY:
373666
show subpopulations
African (AFR)
AF:
0.0552
AC:
1011
AN:
18304
American (AMR)
AF:
0.123
AC:
3931
AN:
32040
Ashkenazi Jewish (ASJ)
AF:
0.300
AC:
5853
AN:
19508
East Asian (EAS)
AF:
0.000368
AC:
12
AN:
32610
South Asian (SAS)
AF:
0.141
AC:
8777
AN:
62320
European-Finnish (FIN)
AF:
0.261
AC:
12235
AN:
46812
Middle Eastern (MID)
AF:
0.291
AC:
1114
AN:
3830
European-Non Finnish (NFE)
AF:
0.224
AC:
103215
AN:
461640
Other (OTH)
AF:
0.200
AC:
7036
AN:
35228
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
5562
11124
16685
22247
27809
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1834
3668
5502
7336
9170
<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:
0.168
AC:
25582
AN:
152224
Hom.:
2652
Cov.:
32
AF XY:
0.169
AC XY:
12596
AN XY:
74422
show subpopulations
African (AFR)
AF:
0.0544
AC:
2259
AN:
41560
American (AMR)
AF:
0.158
AC:
2424
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.310
AC:
1078
AN:
3472
East Asian (EAS)
AF:
0.00154
AC:
8
AN:
5184
South Asian (SAS)
AF:
0.129
AC:
621
AN:
4826
European-Finnish (FIN)
AF:
0.271
AC:
2865
AN:
10580
Middle Eastern (MID)
AF:
0.269
AC:
79
AN:
294
European-Non Finnish (NFE)
AF:
0.230
AC:
15668
AN:
67998
Other (OTH)
AF:
0.201
AC:
423
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1072
2144
3217
4289
5361
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
280
560
840
1120
1400
<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:
0.161
Hom.:
1191
Bravo
AF:
0.154
Asia WGS
AF:
0.0630
AC:
223
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Apr 03, 2019
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

not specified Benign:1
Jan 24, 2024
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.093
DANN
Benign
0.63
PhyloP100
-2.8
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: rs113631743; hg19: chr16-14530726; API