chr1-236550992-T-TAAA

Variant names:

• chr1-236550992-T-TAAA
• rs55866014
• NM_201544.4:c.*2847_*2849dupAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018072.6(HEATR1):​c.6347-5_6347-3dupTTT 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 0.0013 (1 hom., cov: 0)
  • Exomes 𝑓: 0.016 (8 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0162 (18021/1110106) while in subpopulation NFE AF= 0.0177 (15300/864530). AF 95% confidence interval is 0.0175. There are 8 homozygotes in gnomad4_exome. There are 8612 alleles in male gnomad4_exome subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 173 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4	c.*2847_*2849dupAAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000366584.9	NP_963838.1
HEATR1	NM_018072.6	c.6347-5_6347-3dupTTT		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.*2847_*2849dupAAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_201544.4	ENSP00000355543.4
HEATR1	ENST00000366582.8	c.6347-5_6347-3dupTTT		splice_region_variant, intron_variant	Intron 44 of 44	5	NM_018072.6	ENSP00000355541.3

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 173 AN: 137752 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00160

Gnomad ASJ AF: 0.000602

Gnomad EAS AF: 0.00169

Gnomad SAS AF: 0.00475

Gnomad FIN AF: 0.00162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.000541

GnomAD3 exomes AF: 0.0171 AC: 1150 AN: 67430 Hom.: 13 AF XY: 0.0161 AC XY: 565 AN XY: 35072

Gnomad AFR exome AF: 0.00656

Gnomad AMR exome AF: 0.0162

Gnomad ASJ exome AF: 0.0149

Gnomad EAS exome AF: 0.0195

Gnomad SAS exome AF: 0.0116

Gnomad FIN exome AF: 0.0124

Gnomad NFE exome AF: 0.0209

Gnomad OTH exome AF: 0.0213

GnomAD4 exome AF: 0.0162 AC: 18021 AN: 1110106 Hom.: 8 Cov.: 18 AF XY: 0.0156 AC XY: 8612 AN XY: 552284

Gnomad4 AFR exome AF: 0.00604

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.00847

Gnomad4 SAS exome AF: 0.0127

Gnomad4 FIN exome AF: 0.0114

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0131

GnomAD4 genome AF: 0.00126 AC: 173 AN: 137772 Hom.: 1 Cov.: 0 AF XY: 0.00120 AC XY: 79 AN XY: 65754

Gnomad4 AFR AF: 0.00117

Gnomad4 AMR AF: 0.00160

Gnomad4 ASJ AF: 0.000602

Gnomad4 EAS AF: 0.00170

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00162

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.000538

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

LitVar

Other links and lift over

dbSNP: rs55866014; hg19: chr1-236714292;