rs6989

Variant names:

• chr1-236550764-A-C
• rs6989
• NM_018072.6:c.*138T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-236550764-A-C
• chr1-236550764-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HEATR1	NM_018072.6	c.*138T>G		3_prime_UTR_variant	Exon 45 of 45	ENST00000366582.8	NP_060542.4
LGALS8	NM_201544.4	c.*2603A>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000366584.9	NP_963838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR1	ENST00000366582.8	c.*138T>G		3_prime_UTR_variant	Exon 45 of 45	5	NM_018072.6	ENSP00000355541.3
LGALS8	ENST00000366584.9	c.*2603A>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_201544.4	ENSP00000355543.4

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

African (AFR) AF: 0.491 AC: 6217 AN: 12656

American (AMR) AF: 0.536 AC: 8542 AN: 15930

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 8017 AN: 13390

East Asian (EAS) AF: 0.471 AC: 14200 AN: 30148

South Asian (SAS) AF: 0.474 AC: 18600 AN: 39270

European-Finnish (FIN) AF: 0.737 AC: 24711 AN: 33544

Middle Eastern (MID) AF: 0.533 AC: 1610 AN: 3022

European-Non Finnish (NFE) AF: 0.688 AC: 210100 AN: 305446

Other (OTH) AF: 0.632 AC: 16649 AN: 26360

GnomAD4 genome AF: 0.609 AC: 92564 AN: 152016 Hom.: 29123 Cov.: 31 AF XY: 0.606 AC XY: 45048 AN XY: 74316

African (AFR) AF: 0.487 AC: 20209 AN: 41460

American (AMR) AF: 0.571 AC: 8720 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2113 AN: 3468

East Asian (EAS) AF: 0.484 AC: 2497 AN: 5162

South Asian (SAS) AF: 0.459 AC: 2211 AN: 4820

European-Finnish (FIN) AF: 0.751 AC: 7925 AN: 10550

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46918 AN: 67960

Other (OTH) AF: 0.603 AC: 1275 AN: 2114

Alfa AF: 0.642 Hom.: 72937

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
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Other links and lift over

dbSNP: rs6989; hg19: chr1-236714064;