7-69598673-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_015570.4(AUTS2):​c.-981T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 159,586 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 30)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

AUTS2
NM_015570.4 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.378
Variant links:
Genes affected
AUTS2 (HGNC:14262): (activator of transcription and developmental regulator AUTS2) This gene has been implicated in neurodevelopment and as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability, and developmental delay. Mutations in this gene have also been associated with non-neurological disorders, such as acute lymphoblastic leukemia, aging of the skin, early-onset androgenetic alopecia, and certain cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2014]

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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=-0.43).
BP6
Variant 7-69598673-T-C is Benign according to our data. Variant chr7-69598673-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1199522.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00374 (569/152136) while in subpopulation AFR AF= 0.00994 (413/41542). AF 95% confidence interval is 0.00915. There are 3 homozygotes in gnomad4. There are 280 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 569 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AUTS2NM_015570.4 linkuse as main transcriptc.-981T>C 5_prime_UTR_variant 1/19 ENST00000342771.10 NP_056385.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AUTS2ENST00000342771.10 linkuse as main transcriptc.-981T>C 5_prime_UTR_variant 1/191 NM_015570.4 ENSP00000344087 P4Q8WXX7-1
AUTS2ENST00000644939.1 linkuse as main transcriptc.-981T>C 5_prime_UTR_variant 1/19 ENSP00000496726 A1

Frequencies

GnomAD3 genomes
AF:
0.00372
AC:
565
AN:
152026
Hom.:
3
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00987
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00667
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00955
Gnomad NFE
AF:
0.000603
Gnomad OTH
AF:
0.00433
GnomAD4 exome
AF:
0.000134
AC:
1
AN:
7450
Hom.:
0
Cov.:
0
AF XY:
0.000187
AC XY:
1
AN XY:
5360
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000188
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00374
AC:
569
AN:
152136
Hom.:
3
Cov.:
30
AF XY:
0.00376
AC XY:
280
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00994
Gnomad4 AMR
AF:
0.00667
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000603
Gnomad4 OTH
AF:
0.00428
Alfa
AF:
0.00233
Hom.:
1
Bravo
AF:
0.00419
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 24, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
CADD
Benign
17
DANN
Benign
0.76

Splicing

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: rs535154040; hg19: chr7-69063659; API