rs6989

chr1-236550764-A-Cchr1-236550764-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

ACMG classification

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
HEATR1	NM_018072.6	c.*138T>G		3_prime_UTR_variant	45/45	ENST00000366582.8
LGALS8	NM_201544.4	c.*2603A>C		3_prime_UTR_variant	10/10	ENST00000366584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEATR1	ENST00000366582.8	c.*138T>G		3_prime_UTR_variant	45/45	5	NM_018072.6	P1
LGALS8	ENST00000366584.9	c.*2603A>C		3_prime_UTR_variant	10/10	1	NM_201544.4	P1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92509 AN: 151896 Hom.: 29112 Cov.: 31

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

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

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

Other links and lift over

dbSNP: rs6989; hg19: chr1-236714064;