1-236550992-T-TA

Position:

• chr1-236550992-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018072.6(HEATR1):​c.6347-3_6347-2insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (1235 hom., cov: 0)
  • Exomes 𝑓: 0.21 (482 hom.)
• Consequence: HEATR1 NM_018072.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.486

Genes affected

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]

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 -10 ACMG points.

• BP6: Variant 1-236550992-T-TA is Benign according to our data. Variant chr1-236550992-T-TA is described in ClinVar as [Benign]. Clinvar id is 402929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS8	NM_201544.4	c.*2849dup		3_prime_UTR_variant	10/10	ENST00000366584.9	NP_963838.1
HEATR1	NM_018072.6	c.6347-3_6347-2insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000366582.8	NP_060542.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS8	ENST00000366584.9	c.*2849dup		3_prime_UTR_variant	10/10	1	NM_201544.4	ENSP00000355543	P1
HEATR1	ENST00000366582.8	c.6347-3_6347-2insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_018072.6	ENSP00000355541	P1

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 12941 AN: 137708 Hom.: 1237 Cov.: 0

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0185

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.0645

Gnomad EAS AF: 0.00507

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.0938

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0955

GnomAD3 exomes AF: 0.163 AC: 11019 AN: 67430 Hom.: 364 AF XY: 0.163 AC XY: 5707 AN XY: 35072

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.133

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.205 AC: 225049 AN: 1096790 Hom.: 482 Cov.: 18 AF XY: 0.204 AC XY: 111476 AN XY: 545412

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.0940 AC: 12953 AN: 137730 Hom.: 1235 Cov.: 0 AF XY: 0.0940 AC XY: 6177 AN XY: 65730

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.0598

Gnomad4 ASJ AF: 0.0645

Gnomad4 EAS AF: 0.00488

Gnomad4 SAS AF: 0.0620

Gnomad4 FIN AF: 0.0353

Gnomad4 NFE AF: 0.0323

Gnomad4 OTH AF: 0.0955

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

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: rs55866014; hg19: chr1-236714292;