Genetic Variant LGALS8:c.*2842_*2849delAAAAAAAA (chr1-236550992-TAAAAAAAA-T) – 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.6347-10_6347-3delTTTTTTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00616 in 1,255,706 control chromosomes in the GnomAD database, including 299 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.029 ( 173 hom., cov: 0)

Exomes 𝑓: 0.0033 ( 126 hom. )

Consequence

HEATR1
NM_018072.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.48

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4 link	c.2842_2849delAAAAAAAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000366584.9	NP_963838.1	O00214-1
HEATR1	NM_018072.6 link	c.6347-10_6347-3delTTTTTTTT		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.2842_2849delAAAAAAAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_201544.4	ENSP00000355543.4		O00214-1
HEATR1	ENST00000366582.8 link	c.6347-10_6347-3delTTTTTTTT		splice_region_variant, intron_variant	Intron 44 of 44	5	NM_018072.6	ENSP00000355541.3		Q9H583

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

3992

AN:

137798

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0995

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00181

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00119

Gnomad FIN

AF:

0.000147

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000560

Gnomad OTH

AF:

0.0189

GnomAD3 exomes

AF:

0.0214

AC:

1443

AN:

67430

Hom.:

AF XY:

0.0154

AC XY:

540

AN XY:

35072

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000802

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.00956

GnomAD4 exome

AF:

0.00334

AC:

3732

AN:

1117888

Hom.:

126

AF XY:

0.00292

AC XY:

1623

AN XY:

556224

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.00946

Gnomad4 ASJ exome

AF:

0.000210

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000229

Gnomad4 FIN exome

AF:

0.000192

Gnomad4 NFE exome

AF:

0.000353

Gnomad4 OTH exome

AF:

0.00782

GnomAD4 genome

AF:

0.0290

AC:

4001

AN:

137818

Hom.:

173

Cov.:

AF XY:

0.0291

AC XY:

1912

AN XY:

65786

show subpopulations

Gnomad4 AFR

AF:

0.0995

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.00181

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000954

Gnomad4 FIN

AF:

0.000147

Gnomad4 NFE

AF:

0.000560

Gnomad4 OTH

AF:

0.0188

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-TA

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