rs2237189

Variant names:

• chr6-16488125-G-A
• rs2237189
• NM_001128164.2:c.-298-2016C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-16488125-G-A
• chr6-16488125-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128164.2(ATXN1):​c.-298-2016C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 152,118 control chromosomes in the GnomAD database, including 616 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.077 (616 hom., cov: 32)
• Consequence: ATXN1 NM_001128164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 5 publications found

Genes affected

ATXN1 (HGNC:10548): (ataxin 1) The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the `pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. The function of the ataxins is not known. This locus has been mapped to chromosome 6, and it has been determined that the diseased allele contains 40-83 CAG repeats, compared to 6-39 in the normal allele, and is associated with spinocerebellar ataxia type 1 (SCA1). Alternative splicing results in multiple transcript variants, with one variant encoding multiple distinct proteins, ATXN1 and Alt-ATXN1, due to the use of overlapping alternate reading frames. [provided by RefSeq, Nov 2017]

ATXN1 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 1

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN1	NM_001128164.2	c.-298-2016C>T		intron_variant	Intron 5 of 7	ENST00000436367.6	NP_001121636.1
ATXN1	NM_000332.4	c.-298-2016C>T		intron_variant	Intron 6 of 8		NP_000323.2
ATXN1	NM_001357857.2	c.-327-2016C>T		intron_variant	Intron 6 of 8		NP_001344786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN1	ENST00000436367.6	c.-298-2016C>T		intron_variant	Intron 5 of 7	1	NM_001128164.2	ENSP00000416360.1

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11647 AN: 152000 Hom.: 610 Cov.: 32

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0862

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.0731

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0767 AC: 11661 AN: 152118 Hom.: 616 Cov.: 32 AF XY: 0.0783 AC XY: 5825 AN XY: 74366

African (AFR) AF: 0.0576 AC: 2389 AN: 41476

American (AMR) AF: 0.0503 AC: 769 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1090 AN: 5180

South Asian (SAS) AF: 0.167 AC: 804 AN: 4826

European-Finnish (FIN) AF: 0.0862 AC: 912 AN: 10580

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0785 AC: 5338 AN: 67984

Other (OTH) AF: 0.0785 AC: 166 AN: 2114

Alfa AF: 0.0682 Hom.: 375

Bravo AF: 0.0698

Asia WGS AF: 0.189 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.70
PhyloP100		-0.15
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs2237189; hg19: chr6-16488356;