1-236550992-TAAAAAAAAA-TAA

Variant names:

• chr1-236550992-TAAAAAAA-T
• rs55866014
• NM_201544.4:c.*2843_*2849delAAAAAAA

Variant summary

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

The NM_018072.6(HEATR1):​c.6347-9_6347-3delTTTTTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0000143 in 1,255,680 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: 𝑓 0.000015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000014 (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 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS8	NM_201544.4	c.*2843_*2849delAAAAAAA		3_prime_UTR_variant	Exon 10 of 10	ENST00000366584.9	NP_963838.1
HEATR1	NM_018072.6	c.6347-9_6347-3delTTTTTTT		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.*2843_*2849delAAAAAAA		3_prime_UTR_variant	Exon 10 of 10	1	NM_201544.4	ENSP00000355543.4
HEATR1	ENST00000366582.8	c.6347-9_6347-3delTTTTTTT		splice_region_variant, intron_variant	Intron 44 of 44	5	NM_018072.6	ENSP00000355541.3

Frequencies

GnomAD3 genomes AF: 0.0000145 AC: 2 AN: 137788 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000156

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000143 AC: 16 AN: 1117892 Hom.: 0 AF XY: 0.0000144 AC XY: 8 AN XY: 556230

Gnomad4 AFR exome AF: 0.0000383

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000145 AC: 2 AN: 137788 Hom.: 0 Cov.: 0 AF XY: 0.0000304 AC XY: 2 AN XY: 65728

Gnomad4 AFR AF: 0.0000265

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000156

Gnomad4 OTH AF: 0.00

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;