rs2275687

Variant names:

• chr1-236554626-T-C
• rs2275687
• NM_018072.6:c.6050A>G
• HEATR1 p.Glu2017Gly

Variant summary

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

The NM_018072.6(HEATR1):​c.6050A>G​(p.Glu2017Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,610,758 control chromosomes in the GnomAD database, including 355,605 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 0.60 (28249 hom., cov: 31)
  • Exomes 𝑓: 0.66 (327356 hom.)
• Consequence: HEATR1 NM_018072.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.28
• Publications: 44 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 (MetaRNN=5.7085176E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018072.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR1	NM_018072.6	MANE Select	c.6050A>G	p.Glu2017Gly	missense	Exon 42 of 45	NP_060542.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR1	ENST00000366582.8	TSL:5 MANE Select	c.6050A>G	p.Glu2017Gly	missense	Exon 42 of 45	ENSP00000355541.3	Q9H583
	HEATR1	ENST00000927216.1		c.6041A>G	p.Glu2014Gly	missense	Exon 42 of 45	ENSP00000597275.1
	HEATR1	ENST00000366581.6	TSL:5	c.5807A>G	p.Glu1936Gly	missense	Exon 41 of 44	ENSP00000355540.2	Q5T3Q7

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90580 AN: 151828 Hom.: 28240 Cov.: 31

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.600

GnomAD2 exomes AF: 0.609 AC: 151815 AN: 249426 AF XY: 0.609

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.531

Gnomad ASJ exome AF: 0.601

Gnomad EAS exome AF: 0.488

Gnomad FIN exome AF: 0.736

Gnomad NFE exome AF: 0.687

Gnomad OTH exome AF: 0.628

GnomAD4 exome AF: 0.665 AC: 969447 AN: 1458812 Hom.: 327356 Cov.: 38 AF XY: 0.659 AC XY: 478505 AN XY: 725620

African (AFR) AF: 0.431 AC: 14370 AN: 33346

American (AMR) AF: 0.531 AC: 23538 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 15708 AN: 26100

East Asian (EAS) AF: 0.477 AC: 18894 AN: 39642

South Asian (SAS) AF: 0.479 AC: 40967 AN: 85496

European-Finnish (FIN) AF: 0.739 AC: 39463 AN: 53388

Middle Eastern (MID) AF: 0.544 AC: 3137 AN: 5764

European-Non Finnish (NFE) AF: 0.698 AC: 775005 AN: 1110484

Other (OTH) AF: 0.636 AC: 38365 AN: 60302

GnomAD4 genome AF: 0.596 AC: 90630 AN: 151946 Hom.: 28249 Cov.: 31 AF XY: 0.595 AC XY: 44151 AN XY: 74264

African (AFR) AF: 0.442 AC: 18294 AN: 41400

American (AMR) AF: 0.568 AC: 8671 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2112 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2500 AN: 5154

South Asian (SAS) AF: 0.460 AC: 2217 AN: 4820

European-Finnish (FIN) AF: 0.753 AC: 7942 AN: 10552

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.691 AC: 46940 AN: 67964

Other (OTH) AF: 0.598 AC: 1260 AN: 2108

Alfa AF: 0.642 Hom.: 94695

Bravo AF: 0.574

Asia WGS AF: 0.450 AC: 1569 AN: 3478

EpiCase AF: 0.673

EpiControl AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0000057	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.28
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0090	D
Varity_R		0.54
gMVP		0.43
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2275687;

hg19: chr1-236717926;

COSMIC: COSV63979833;

COSMIC: COSV63979833;