Genetic Variant LGALS8:c.*2848_*2849dupAA (chr1-236550992-T-TAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018072.6(HEATR1):c.6347-4_6347-3dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 20878 hom., cov: 0)

Exomes 𝑓: 0.32 ( 2158 hom. )

Failed GnomAD Quality Control

Consequence

HEATR1
NM_018072.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.486

Variant links:

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]

LGALS8 links:

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]

HEATR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4 link	c.2848_2849dupAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000366584.9	NP_963838.1	O00214-1
HEATR1	NM_018072.6 link	c.6347-4_6347-3dupTT		splice_region_variant, intron_variant	Intron 44 of 44	ENST00000366582.8	NP_060542.4	Q9H583A2VDI1B2RWN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS8	ENST00000366584.9 link	c.2848_2849dupAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_201544.4	ENSP00000355543.4		O00214-1
HEATR1	ENST00000366582.8 link	c.6347-4_6347-3dupTT		splice_region_variant, intron_variant	Intron 44 of 44	5	NM_018072.6	ENSP00000355541.3		Q9H583

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

72600

AN:

137352

Hom.:

20886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.687

Gnomad MID

AF:

0.469

Gnomad NFE

AF:

0.660

Gnomad OTH

AF:

0.528

GnomAD3 exomes

AF:

0.189

AC:

12774

AN:

67430

Hom.:

182

AF XY:

0.186

AC XY:

6533

AN XY:

35072

show subpopulations

Gnomad AFR exome

AF:

0.0969

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.212

Gnomad SAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.315

AC:

338529

AN:

1073724

Hom.:

2158

Cov.:

AF XY:

0.313

AC XY:

166658

AN XY:

533016

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.221

Gnomad4 FIN exome

AF:

0.352

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.528

AC:

72579

AN:

137372

Hom.:

20878

Cov.:

AF XY:

0.524

AC XY:

34339

AN XY:

65540

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.521

Gnomad4 ASJ

AF:

0.547

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.437

Gnomad4 FIN

AF:

0.687

Gnomad4 NFE

AF:

0.660

Gnomad4 OTH

AF:

0.528

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

1-236550992-TAAAAAAAAA-TAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over