1-236550992-TAAAAAAAAA-TAAAAAAA

Variant names:

• chr1-236550992-TAA-T
• rs55866014
• NM_201544.4:c.*2848_*2849delAA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_018072.6(HEATR1):​c.6347-4_6347-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00847 in 1,239,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0095 (0 hom.)
• Consequence: HEATR1 NM_018072.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 -9 ACMG points.

• BP6: Variant 1-236550992-TAA-T is Benign according to our data. Variant chr1-236550992-TAA-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00953 (10496/1101922) while in subpopulation AMR AF= 0.0234 (538/22972). AF 95% confidence interval is 0.0218. There are 0 homozygotes in gnomad4_exome. There are 5334 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4	c.*2848_*2849delAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000366584.9	NP_963838.1
HEATR1	NM_018072.6	c.6347-4_6347-3delTT		splice_region_variant, intron_variant	Intron 44 of 44	ENST00000366582.8	NP_060542.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS8	ENST00000366584.9	c.*2848_*2849delAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_201544.4	ENSP00000355543.4
HEATR1	ENST00000366582.8	c.6347-4_6347-3delTT		splice_region_variant, intron_variant	Intron 44 of 44	5	NM_018072.6	ENSP00000355541.3

Frequencies

GnomAD3 genomes AF: 0.0000726 AC: 10 AN: 137774 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000727

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000293

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000467

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0353 AC: 2381 AN: 67430 Hom.: 0 AF XY: 0.0368 AC XY: 1291 AN XY: 35072

Gnomad AFR exome AF: 0.0220

Gnomad AMR exome AF: 0.0382

Gnomad ASJ exome AF: 0.0369

Gnomad EAS exome AF: 0.0389

Gnomad SAS exome AF: 0.0495

Gnomad FIN exome AF: 0.0437

Gnomad NFE exome AF: 0.0328

Gnomad OTH exome AF: 0.0298

GnomAD4 exome AF: 0.00953 AC: 10496 AN: 1101922 Hom.: 0 AF XY: 0.00974 AC XY: 5334 AN XY: 547850

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.0234

Gnomad4 ASJ exome AF: 0.0145

Gnomad4 EAS exome AF: 0.0142

Gnomad4 SAS exome AF: 0.0189

Gnomad4 FIN exome AF: 0.00623

Gnomad4 NFE exome AF: 0.00823

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.0000726 AC: 10 AN: 137774 Hom.: 0 Cov.: 0 AF XY: 0.0000913 AC XY: 6 AN XY: 65720

Gnomad4 AFR AF: 0.000106

Gnomad4 AMR AF: 0.0000727

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000293

Gnomad4 NFE AF: 0.0000467

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;