rs959175

Positions:

• chr1-236589582-T-C
• chr1-236589582-T-G

Variant summary

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

The NM_018072.6(HEATR1):​c.1530+1265A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,982 control chromosomes in the GnomAD database, including 24,032 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 0.54 (24032 hom., cov: 32)
• Consequence: HEATR1 NM_018072.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEATR1	NM_018072.6	c.1530+1265A>G		intron_variant		ENST00000366582.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEATR1	ENST00000366582.8	c.1530+1265A>G		intron_variant		5	NM_018072.6	P1
HEATR1	ENST00000366581.6	c.1530+1265A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81885 AN: 151864 Hom.: 24030 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.544

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.539 AC: 81918 AN: 151982 Hom.: 24032 Cov.: 32 AF XY: 0.540 AC XY: 40087 AN XY: 74270

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.543

Alfa AF: 0.600 Hom.: 3560

Bravo AF: 0.511

Asia WGS AF: 0.439 AC: 1528 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.68

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: rs959175; hg19: chr1-236752882;