1-236550992-TAAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr1-236550992-T-TA
• rs55866014
• NM_201544.4:c.*2849dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018072.6(HEATR1):​c.6347-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (1235 hom., cov: 0)
  • Exomes 𝑓: 0.21 (482 hom.)
• Consequence: HEATR1 NM_018072.6 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 1-236550992-T-TA is Benign according to our data. Variant chr1-236550992-T-TA is described in ClinVar as Benign. ClinVar VariationId is 402929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 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.*2849dupA		3_prime_UTR	Exon 10 of 10	NP_963838.1	O00214-1
	HEATR1	NM_018072.6	MANE Select	c.6347-3dupT		splice_region intron	N/A	NP_060542.4
	LGALS8	NM_006499.5		c.*2849dupA		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.*2849dupA		3_prime_UTR	Exon 10 of 10	ENSP00000355543.4	O00214-1
	LGALS8	ENST00000450372.6	TSL:1	c.*2849dupA		3_prime_UTR	Exon 12 of 12	ENSP00000408657.2	O00214-2
	HEATR1	ENST00000366582.8	TSL:5 MANE Select	c.6347-3dupT		splice_region intron	N/A	ENSP00000355541.3	Q9H583

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 12941 AN: 137708 Hom.: 1237 Cov.: 0

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0185

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.0645

Gnomad EAS AF: 0.00507

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.0353

Gnomad MID AF: 0.0938

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0955

GnomAD2 exomes AF: 0.163 AC: 11019 AN: 67430 AF XY: 0.163

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.133

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.205 AC: 225049 AN: 1096790 Hom.: 482 Cov.: 18 AF XY: 0.204 AC XY: 111476 AN XY: 545412

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.216 AC: 5510 AN: 25454

American (AMR) AF: 0.154 AC: 3617 AN: 23458

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 3529 AN: 18708

East Asian (EAS) AF: 0.135 AC: 4525 AN: 33604

South Asian (SAS) AF: 0.159 AC: 9570 AN: 60070

European-Finnish (FIN) AF: 0.232 AC: 7058 AN: 30368

Middle Eastern (MID) AF: 0.166 AC: 636 AN: 3838

European-Non Finnish (NFE) AF: 0.212 AC: 181185 AN: 854122

Other (OTH) AF: 0.200 AC: 9419 AN: 47168

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0940 AC: 12953 AN: 137730 Hom.: 1235 Cov.: 0 AF XY: 0.0940 AC XY: 6177 AN XY: 65730

African (AFR) AF: 0.241 AC: 9098 AN: 37698

American (AMR) AF: 0.0598 AC: 822 AN: 13752

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 214 AN: 3320

East Asian (EAS) AF: 0.00488 AC: 23 AN: 4714

South Asian (SAS) AF: 0.0620 AC: 260 AN: 4194

European-Finnish (FIN) AF: 0.0353 AC: 241 AN: 6820

Middle Eastern (MID) AF: 0.0985 AC: 26 AN: 264

European-Non Finnish (NFE) AF: 0.0323 AC: 2075 AN: 64240

Other (OTH) AF: 0.0955 AC: 178 AN: 1864

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: COSV59383539; COSMIC: COSV59383539;