Variant 6-16326380-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001128164.2(ATXN1):c.1917+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,611,262 control chromosomes in the GnomAD database, including 1,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 479 hom., cov: 32)

Exomes 𝑓: 0.013 ( 583 hom. )

Consequence

ATXN1
NM_001128164.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.69

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-16326380-C-A is Benign according to our data. Variant chr6-16326380-C-A is described in ClinVar as [Benign]. Clinvar id is 1304636.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ATXN1	NM_001128164.2 linkuse as main transcript	c.1917+14G>T	intron_variant	ENST00000436367.6
ATXN1	NM_000332.4 linkuse as main transcript	c.1917+14G>T	intron_variant
ATXN1	NM_001357857.2 linkuse as main transcript	c.*1330+14G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN1	ENST00000436367.6 linkuse as main transcript	c.1917+14G>T		intron_variant		1	NM_001128164.2	P1	P54253-1
ATXN1	ENST00000244769.8 linkuse as main transcript	c.1917+14G>T		intron_variant		1		P1	P54253-1

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7506

AN:

152110

Hom.:

471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0224

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.00731

Gnomad SAS

AF:

0.00914

Gnomad FIN

AF:

0.00640

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00841

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0203

AC:

5059

AN:

249326

Hom.:

214

AF XY:

0.0176

AC XY:

2379

AN XY:

134862

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.0451

Gnomad EAS exome

AF:

0.00620

Gnomad SAS exome

AF:

0.00938

Gnomad FIN exome

AF:

0.00742

Gnomad NFE exome

AF:

0.00912

Gnomad OTH exome

AF:

0.0172

GnomAD4 exome

AF:

0.0125

AC:

18250

AN:

1459034

Hom.:

583

Cov.:

AF XY:

0.0123

AC XY:

8892

AN XY:

725580

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.0140

Gnomad4 ASJ exome

AF:

0.0450

Gnomad4 EAS exome

AF:

0.00595

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.00636

Gnomad4 NFE exome

AF:

0.00719

Gnomad4 OTH exome

AF:

0.0209

GnomAD4 genome

AF:

0.0495

AC:

7538

AN:

152228

Hom.:

479

Cov.:

AF XY:

0.0480

AC XY:

3573

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.0224

Gnomad4 ASJ

AF:

0.0418

Gnomad4 EAS

AF:

0.00733

Gnomad4 SAS

AF:

0.00873

Gnomad4 FIN

AF:

0.00640

Gnomad4 NFE

AF:

0.00841

Gnomad4 OTH

AF:

0.0482

Alfa

AF:

0.0240

Hom.:

Bravo

AF:

0.0550

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.0060

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over