1-236550992-TAAAAAAAAA-TAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018072.6(HEATR1):​c.6347-4_6347-3dupTT 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 0.53 (20878 hom., cov: 0)
  • Exomes 𝑓: 0.32 (2158 hom.)
  • Failed GnomAD Quality Control
• Consequence: HEATR1 NM_018072.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018072.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	NM_201544.4	MANE Select	c.*2848_*2849dupAA		3_prime_UTR	Exon 10 of 10	NP_963838.1	O00214-1
	HEATR1	NM_018072.6	MANE Select	c.6347-4_6347-3dupTT		splice_region intron	N/A	NP_060542.4
	LGALS8	NM_006499.5		c.*2848_*2849dupAA		3_prime_UTR	Exon 12 of 12	NP_006490.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS8	ENST00000366584.9	TSL:1 MANE Select	c.*2848_*2849dupAA		3_prime_UTR	Exon 10 of 10	ENSP00000355543.4	O00214-1
	LGALS8	ENST00000450372.6	TSL:1	c.*2848_*2849dupAA		3_prime_UTR	Exon 12 of 12	ENSP00000408657.2	O00214-2
	HEATR1	ENST00000366582.8	TSL:5 MANE Select	c.6347-4_6347-3dupTT		splice_region intron	N/A	ENSP00000355541.3	Q9H583

Frequencies

GnomAD3 genomes AF: 0.529 AC: 72600 AN: 137352 Hom.: 20886 Cov.: 0

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.469

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.528

GnomAD2 exomes AF: 0.189 AC: 12774 AN: 67430 AF XY: 0.186

Gnomad AFR exome AF: 0.0969

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.212

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.226

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.315 AC: 338529 AN: 1073724 Hom.: 2158 Cov.: 18 AF XY: 0.313 AC XY: 166658 AN XY: 533016

African (AFR) AF: 0.142 AC: 3582 AN: 25144

American (AMR) AF: 0.210 AC: 4755 AN: 22656

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 4811 AN: 18028

East Asian (EAS) AF: 0.240 AC: 7638 AN: 31762

South Asian (SAS) AF: 0.221 AC: 12809 AN: 57922

European-Finnish (FIN) AF: 0.352 AC: 10391 AN: 29488

Middle Eastern (MID) AF: 0.226 AC: 847 AN: 3750

European-Non Finnish (NFE) AF: 0.334 AC: 279905 AN: 839076

Other (OTH) AF: 0.300 AC: 13791 AN: 45898

GnomAD4 genome AF: 0.528 AC: 72579 AN: 137372 Hom.: 20878 Cov.: 0 AF XY: 0.524 AC XY: 34339 AN XY: 65540

African (AFR) AF: 0.291 AC: 10931 AN: 37618

American (AMR) AF: 0.521 AC: 7145 AN: 13710

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1811 AN: 3310

East Asian (EAS) AF: 0.486 AC: 2282 AN: 4692

South Asian (SAS) AF: 0.437 AC: 1828 AN: 4180

European-Finnish (FIN) AF: 0.687 AC: 4685 AN: 6820

Middle Eastern (MID) AF: 0.466 AC: 122 AN: 262

European-Non Finnish (NFE) AF: 0.660 AC: 42294 AN: 64064

Other (OTH) AF: 0.528 AC: 978 AN: 1854

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs55866014; hg19: chr1-236714292; COSMIC: COSV59381124; COSMIC: COSV59381124;