rs3821902

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377405.1(ATXN7):​c.499+3538T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,252 control chromosomes in the GnomAD database, including 1,061 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 0.11 ( 1061 hom., cov: 31)

Consequence

ATXN7
NM_001377405.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.62
Variant links:
Genes affected
ATXN7 (HGNC:10560): (ataxin 7) 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. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATXN7NM_001377405.1 linkuse as main transcriptc.499+3538T>G intron_variant ENST00000674280.1
ATXN7NM_000333.4 linkuse as main transcriptc.499+3538T>G intron_variant
ATXN7NM_001177387.1 linkuse as main transcriptc.499+3538T>G intron_variant
ATXN7NM_001377406.1 linkuse as main transcriptc.499+3538T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATXN7ENST00000674280.1 linkuse as main transcriptc.499+3538T>G intron_variant NM_001377405.1 P2O15265-1

Frequencies

GnomAD3 genomes
AF:
0.107
AC:
16354
AN:
152134
Hom.:
1060
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0412
Gnomad AMI
AF:
0.0537
Gnomad AMR
AF:
0.158
Gnomad ASJ
AF:
0.173
Gnomad EAS
AF:
0.144
Gnomad SAS
AF:
0.123
Gnomad FIN
AF:
0.0640
Gnomad MID
AF:
0.149
Gnomad NFE
AF:
0.136
Gnomad OTH
AF:
0.134
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.107
AC:
16360
AN:
152252
Hom.:
1061
Cov.:
31
AF XY:
0.106
AC XY:
7859
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0412
Gnomad4 AMR
AF:
0.158
Gnomad4 ASJ
AF:
0.173
Gnomad4 EAS
AF:
0.145
Gnomad4 SAS
AF:
0.124
Gnomad4 FIN
AF:
0.0640
Gnomad4 NFE
AF:
0.136
Gnomad4 OTH
AF:
0.133
Alfa
AF:
0.132
Hom.:
831
Bravo
AF:
0.115
Asia WGS
AF:
0.107
AC:
375
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.023
DANN
Benign
0.42

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs3821902; hg19: chr3-63941697; API