1-236584591-C-T

Variant names:

• chr1-236584591-C-T
• rs2794766
• NM_018072.6:c.2241+434G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018072.6(HEATR1):​c.2241+434G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,890 control chromosomes in the GnomAD database, including 28,008 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 0.59 (28008 hom., cov: 32)
• Consequence: HEATR1 NM_018072.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR1	NM_018072.6	c.2241+434G>A		intron_variant	Intron 17 of 44	ENST00000366582.8	NP_060542.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR1	ENST00000366582.8	c.2241+434G>A		intron_variant	Intron 17 of 44	5	NM_018072.6	ENSP00000355541.3
HEATR1	ENST00000366581.6	c.2241+434G>A		intron_variant	Intron 17 of 43	5		ENSP00000355540.2

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89265 AN: 151772 Hom.: 28013 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.588 AC: 89292 AN: 151890 Hom.: 28008 Cov.: 32 AF XY: 0.587 AC XY: 43599 AN XY: 74250

African (AFR) AF: 0.364 AC: 15050 AN: 41382

American (AMR) AF: 0.616 AC: 9408 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2225 AN: 3464

East Asian (EAS) AF: 0.625 AC: 3226 AN: 5164

South Asian (SAS) AF: 0.502 AC: 2415 AN: 4810

European-Finnish (FIN) AF: 0.744 AC: 7844 AN: 10542

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47115 AN: 67948

Other (OTH) AF: 0.617 AC: 1300 AN: 2108

Alfa AF: 0.636 Hom.: 3827

Bravo AF: 0.569

Asia WGS AF: 0.556 AC: 1931 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.3
DANN	Benign	0.44
PhyloP100		0.0080
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: rs2794766; hg19: chr1-236747891;