rs2275687

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018072.6(HEATR1):ā€‹c.6050A>Gā€‹(p.Glu2017Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,610,758 control chromosomes in the GnomAD database, including 355,605 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.60 ( 28249 hom., cov: 31)
Exomes š‘“: 0.66 ( 327356 hom. )

Consequence

HEATR1
NM_018072.6 missense

Scores

2
6
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.28
Variant links:
Genes affected
HEATR1 (HGNC:25517): (HEAT repeat containing 1) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in fibrillar center and mitochondrion. Implicated in pancreatic ductal carcinoma. Biomarker of glioblastoma. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=5.7085176E-6).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HEATR1NM_018072.6 linkuse as main transcriptc.6050A>G p.Glu2017Gly missense_variant 42/45 ENST00000366582.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HEATR1ENST00000366582.8 linkuse as main transcriptc.6050A>G p.Glu2017Gly missense_variant 42/455 NM_018072.6 P1
HEATR1ENST00000366581.6 linkuse as main transcriptc.5807A>G p.Glu1936Gly missense_variant 41/445

Frequencies

GnomAD3 genomes
AF:
0.597
AC:
90580
AN:
151828
Hom.:
28240
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.442
Gnomad AMI
AF:
0.593
Gnomad AMR
AF:
0.568
Gnomad ASJ
AF:
0.609
Gnomad EAS
AF:
0.485
Gnomad SAS
AF:
0.460
Gnomad FIN
AF:
0.753
Gnomad MID
AF:
0.532
Gnomad NFE
AF:
0.691
Gnomad OTH
AF:
0.600
GnomAD3 exomes
AF:
0.609
AC:
151815
AN:
249426
Hom.:
47732
AF XY:
0.609
AC XY:
82062
AN XY:
134704
show subpopulations
Gnomad AFR exome
AF:
0.435
Gnomad AMR exome
AF:
0.531
Gnomad ASJ exome
AF:
0.601
Gnomad EAS exome
AF:
0.488
Gnomad SAS exome
AF:
0.473
Gnomad FIN exome
AF:
0.736
Gnomad NFE exome
AF:
0.687
Gnomad OTH exome
AF:
0.628
GnomAD4 exome
AF:
0.665
AC:
969447
AN:
1458812
Hom.:
327356
Cov.:
38
AF XY:
0.659
AC XY:
478505
AN XY:
725620
show subpopulations
Gnomad4 AFR exome
AF:
0.431
Gnomad4 AMR exome
AF:
0.531
Gnomad4 ASJ exome
AF:
0.602
Gnomad4 EAS exome
AF:
0.477
Gnomad4 SAS exome
AF:
0.479
Gnomad4 FIN exome
AF:
0.739
Gnomad4 NFE exome
AF:
0.698
Gnomad4 OTH exome
AF:
0.636
GnomAD4 genome
AF:
0.596
AC:
90630
AN:
151946
Hom.:
28249
Cov.:
31
AF XY:
0.595
AC XY:
44151
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.442
Gnomad4 AMR
AF:
0.568
Gnomad4 ASJ
AF:
0.609
Gnomad4 EAS
AF:
0.485
Gnomad4 SAS
AF:
0.460
Gnomad4 FIN
AF:
0.753
Gnomad4 NFE
AF:
0.691
Gnomad4 OTH
AF:
0.598
Alfa
AF:
0.656
Hom.:
69506
Bravo
AF:
0.574
TwinsUK
AF:
0.704
AC:
2610
ALSPAC
AF:
0.696
AC:
2684
ESP6500AA
AF:
0.443
AC:
1951
ESP6500EA
AF:
0.683
AC:
5871
ExAC
AF:
0.606
AC:
73516
Asia WGS
AF:
0.450
AC:
1569
AN:
3478
EpiCase
AF:
0.673
EpiControl
AF:
0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.025
T;.
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.66
T;T
MetaRNN
Benign
0.0000057
T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
7.6e-7
P;P
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Benign
0.28
Sift
Uncertain
0.013
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
D;B
Vest4
0.24
MPC
0.21
ClinPred
0.030
T
GERP RS
5.7
Varity_R
0.54
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2275687; hg19: chr1-236717926; COSMIC: COSV63979833; COSMIC: COSV63979833; API