NM_001128164.2:c.-160-15991A>G

Variant names:

• chr6-16344461-T-C
• rs179986
• NM_001128164.2:c.-160-15991A>G

Variant summary

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

The NM_001128164.2(ATXN1):​c.-160-15991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,134 control chromosomes in the GnomAD database, including 44,513 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 0.76 (44513 hom., cov: 32)
• Consequence: ATXN1 NM_001128164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 1 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN1	NM_001128164.2	c.-160-15991A>G		intron_variant	Intron 6 of 7	ENST00000436367.6	NP_001121636.1
ATXN1	NM_000332.4	c.-160-15991A>G		intron_variant	Intron 7 of 8		NP_000323.2
ATXN1	NM_001357857.2	c.-189-15991A>G		intron_variant	Intron 7 of 8		NP_001344786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN1	ENST00000436367.6	c.-160-15991A>G		intron_variant	Intron 6 of 7	1	NM_001128164.2	ENSP00000416360.1
ATXN1	ENST00000244769.8	c.-160-15991A>G		intron_variant	Intron 7 of 8	1		ENSP00000244769.3

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115054 AN: 152016 Hom.: 44452 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.757 AC: 115174 AN: 152134 Hom.: 44513 Cov.: 32 AF XY: 0.758 AC XY: 56358 AN XY: 74368

African (AFR) AF: 0.894 AC: 37104 AN: 41500

American (AMR) AF: 0.792 AC: 12106 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2192 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5172 AN: 5188

South Asian (SAS) AF: 0.764 AC: 3694 AN: 4832

European-Finnish (FIN) AF: 0.633 AC: 6678 AN: 10556

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45800 AN: 67988

Other (OTH) AF: 0.746 AC: 1577 AN: 2114

Alfa AF: 0.712 Hom.: 4582

Bravo AF: 0.777

Asia WGS AF: 0.898 AC: 3123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.5
DANN	Benign	0.94
PhyloP100		-0.63
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: rs179986; hg19: chr6-16344692;