1-236550992-TAAAAAAAAA-TAAAAAAAA

Variant names:

• chr1-236550992-TA-T
• rs55866014
• NM_201544.4:c.*2849delA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_018072.6(HEATR1):​c.6347-3delT variant causes a splice region, 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 Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0058 (1 hom., cov: 0)
  • Exomes 𝑓: 0.093 (1 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-TA-T is Benign according to our data. Variant chr1-236550992-TA-T is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4	c.*2849delA		3_prime_UTR_variant	Exon 10 of 10	ENST00000366584.9	NP_963838.1
HEATR1	NM_018072.6	c.6347-3delT		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.*2849delA		3_prime_UTR_variant	Exon 10 of 10	1	NM_201544.4	ENSP00000355543.4
HEATR1	ENST00000366582.8	c.6347-3delT		splice_region_variant, intron_variant	Intron 44 of 44	5	NM_018072.6	ENSP00000355541.3

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 803 AN: 137752 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00771

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00148

Gnomad SAS AF: 0.00261

Gnomad FIN AF: 0.00808

Gnomad MID AF: 0.0278

Gnomad NFE AF: 0.00574

Gnomad OTH AF: 0.00811

GnomAD3 exomes AF: 0.194 AC: 13073 AN: 67430 Hom.: 0 AF XY: 0.200 AC XY: 7001 AN XY: 35072

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.211

Gnomad SAS exome AF: 0.241

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.0929 AC: 101516 AN: 1092986 Hom.: 1 Cov.: 18 AF XY: 0.0943 AC XY: 51235 AN XY: 543148

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.0750

Gnomad4 NFE exome AF: 0.0834

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.00584 AC: 804 AN: 137768 Hom.: 1 Cov.: 0 AF XY: 0.00583 AC XY: 383 AN XY: 65748

Gnomad4 AFR AF: 0.00493

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00148

Gnomad4 SAS AF: 0.00262

Gnomad4 FIN AF: 0.00808

Gnomad4 NFE AF: 0.00574

Gnomad4 OTH AF: 0.00806

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;