NM_018072.6:c.5754+6G>T

Variant names:

• chr1-236555545-C-A
• NM_018072.6:c.5754+6G>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018072.6(HEATR1):​c.5754+6G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: HEATR1 NM_018072.6 splice_region, intron
• Scores: Splicing: ADA: 0.00001983
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR1	NM_018072.6	c.5754+6G>T		splice_region_variant, intron_variant	Intron 40 of 44	ENST00000366582.8	NP_060542.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR1	ENST00000366582.8	c.5754+6G>T		splice_region_variant, intron_variant	Intron 40 of 44	5	NM_018072.6	ENSP00000355541.3
HEATR1	ENST00000366581.6	c.5511+6G>T		splice_region_variant, intron_variant	Intron 39 of 43	5		ENSP00000355540.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461742 Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4 AN XY: 727190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.5
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0060
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-236718845;