1-236550992-TAAAAAAAAA-TAAAA

Variant names:

• chr1-236550992-TAAAAA-T
• NM_201544.4:c.*2845_*2849delAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018072.6(HEATR1):​c.6347-7_6347-3delTTTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000188 in 1,117,844 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: HEATR1 NM_018072.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4	c.*2845_*2849delAAAAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000366584.9	NP_963838.1
HEATR1	NM_018072.6	c.6347-7_6347-3delTTTTT		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.*2845_*2849delAAAAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_201544.4	ENSP00000355543.4
HEATR1	ENST00000366582.8	c.6347-7_6347-3delTTTTT		splice_region_variant, intron_variant	Intron 44 of 44	5	NM_018072.6	ENSP00000355541.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000188 AC: 21 AN: 1117844 Hom.: 0 AF XY: 0.0000180 AC XY: 10 AN XY: 556198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000292

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000218

Gnomad4 OTH exome AF: 0.0000208

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-236714292;