1-236550992-TAAAAAAAAA-TA

Variant names:

• chr1-236550992-TAAAAAAAA-T
• rs55866014
• NM_201544.4:c.*2842_*2849delAAAAAAAA

Variant summary

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

The NM_018072.6(HEATR1):​c.6347-10_6347-3delTTTTTTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00616 in 1,255,706 control chromosomes in the GnomAD database, including 299 homozygotes. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.029 (173 hom., cov: 0)
  • Exomes 𝑓: 0.0033 (126 hom.)
• Consequence: HEATR1 NM_018072.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48
• 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 (AFR) allele frequency at 95% confidence interval = 0.0969 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.*2842_*2849delAAAAAAAA		3_prime_UTR	Exon 10 of 10	NP_963838.1	O00214-1
	HEATR1	NM_018072.6	MANE Select	c.6347-10_6347-3delTTTTTTTT		splice_region intron	N/A	NP_060542.4
	LGALS8	NM_006499.5		c.*2842_*2849delAAAAAAAA		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.*2842_*2849delAAAAAAAA		3_prime_UTR	Exon 10 of 10	ENSP00000355543.4	O00214-1
	LGALS8	ENST00000450372.6	TSL:1	c.*2842_*2849delAAAAAAAA		3_prime_UTR	Exon 12 of 12	ENSP00000408657.2	O00214-2
	HEATR1	ENST00000366582.8	TSL:5 MANE Select	c.6347-10_6347-3delTTTTTTTT		splice_region intron	N/A	ENSP00000355541.3	Q9H583

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 3992 AN: 137798 Hom.: 172 Cov.: 0

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00181

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00119

Gnomad FIN AF: 0.000147

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000560

Gnomad OTH AF: 0.0189

GnomAD2 exomes AF: 0.0214 AC: 1443 AN: 67430 AF XY: 0.0154

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000802

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.00956

GnomAD4 exome AF: 0.00334 AC: 3732 AN: 1117888 Hom.: 126 AF XY: 0.00292 AC XY: 1623 AN XY: 556224

African (AFR) AF: 0.106 AC: 2758 AN: 26088

American (AMR) AF: 0.00946 AC: 225 AN: 23786

Ashkenazi Jewish (ASJ) AF: 0.000210 AC: 4 AN: 19030

East Asian (EAS) AF: 0.00 AC: 0 AN: 34238

South Asian (SAS) AF: 0.000229 AC: 14 AN: 61164

European-Finnish (FIN) AF: 0.000192 AC: 6 AN: 31256

Middle Eastern (MID) AF: 0.0108 AC: 42 AN: 3894

European-Non Finnish (NFE) AF: 0.000353 AC: 307 AN: 870364

Other (OTH) AF: 0.00782 AC: 376 AN: 48068

GnomAD4 genome AF: 0.0290 AC: 4001 AN: 137818 Hom.: 173 Cov.: 0 AF XY: 0.0291 AC XY: 1912 AN XY: 65786

African (AFR) AF: 0.0995 AC: 3760 AN: 37770

American (AMR) AF: 0.0116 AC: 159 AN: 13760

Ashkenazi Jewish (ASJ) AF: 0.00181 AC: 6 AN: 3322

East Asian (EAS) AF: 0.00 AC: 0 AN: 4716

South Asian (SAS) AF: 0.000954 AC: 4 AN: 4192

European-Finnish (FIN) AF: 0.000147 AC: 1 AN: 6822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.000560 AC: 36 AN: 64246

Other (OTH) AF: 0.0188 AC: 35 AN: 1862

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=96/4	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;