rs6989

Variant summary

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

The NM_018072.6(HEATR1):​c.*138T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 631,782 control chromosomes in the GnomAD database, including 130,576 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 0.61 ( 29123 hom., cov: 31)
Exomes 𝑓: 0.64 ( 101453 hom. )

Consequence

HEATR1
NM_018072.6 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18
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]
LGALS8 (HGNC:6569): (galectin 8) This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
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.*138T>G 3_prime_UTR_variant 45/45 ENST00000366582.8
LGALS8NM_201544.4 linkuse as main transcriptc.*2603A>C 3_prime_UTR_variant 10/10 ENST00000366584.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HEATR1ENST00000366582.8 linkuse as main transcriptc.*138T>G 3_prime_UTR_variant 45/455 NM_018072.6 P1
LGALS8ENST00000366584.9 linkuse as main transcriptc.*2603A>C 3_prime_UTR_variant 10/101 NM_201544.4 P1O00214-1

Frequencies

GnomAD3 genomes
AF:
0.609
AC:
92509
AN:
151896
Hom.:
29112
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.487
Gnomad AMI
AF:
0.594
Gnomad AMR
AF:
0.571
Gnomad ASJ
AF:
0.609
Gnomad EAS
AF:
0.483
Gnomad SAS
AF:
0.458
Gnomad FIN
AF:
0.751
Gnomad MID
AF:
0.525
Gnomad NFE
AF:
0.690
Gnomad OTH
AF:
0.605
GnomAD4 exome
AF:
0.643
AC:
308646
AN:
479766
Hom.:
101453
Cov.:
6
AF XY:
0.636
AC XY:
160875
AN XY:
252940
show subpopulations
Gnomad4 AFR exome
AF:
0.491
Gnomad4 AMR exome
AF:
0.536
Gnomad4 ASJ exome
AF:
0.599
Gnomad4 EAS exome
AF:
0.471
Gnomad4 SAS exome
AF:
0.474
Gnomad4 FIN exome
AF:
0.737
Gnomad4 NFE exome
AF:
0.688
Gnomad4 OTH exome
AF:
0.632
GnomAD4 genome
AF:
0.609
AC:
92564
AN:
152016
Hom.:
29123
Cov.:
31
AF XY:
0.606
AC XY:
45048
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.487
Gnomad4 AMR
AF:
0.571
Gnomad4 ASJ
AF:
0.609
Gnomad4 EAS
AF:
0.484
Gnomad4 SAS
AF:
0.459
Gnomad4 FIN
AF:
0.751
Gnomad4 NFE
AF:
0.690
Gnomad4 OTH
AF:
0.603
Alfa
AF:
0.659
Hom.:
49107
Bravo
AF:
0.589
Asia WGS
AF:
0.452
AC:
1575
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.8
DANN
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

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

Other links and lift over

dbSNP: rs6989; hg19: chr1-236714064; API