dbSNP rs10486876: AUTS2:c.661-60570T>C (chr7-70375182-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015570.4(AUTS2):c.661-60570T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,222 control chromosomes in the GnomAD database, including 2,519 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 0.14 ( 2519 hom., cov: 32)

Consequence

AUTS2
NM_015570.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.339

Publications

2 publications found

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]

AUTS2 Gene-Disease associations (from GenCC):

autism spectrum disorder due to AUTS2 deficiency
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

AUTS2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_015570.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.661-60570T>C		intron	N/A	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.661-60570T>C		intron	N/A	NP_001120703.1	Q8WXX7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.661-60570T>C	intron	N/A	ENSP00000344087.4	Q8WXX7-1
AUTS2	ENST00000406775.6	TSL:1	c.661-60570T>C	intron	N/A	ENSP00000385263.2	Q8WXX7-2
AUTS2	ENST00000644939.1		c.661-60570T>C	intron	N/A	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20760

AN:

152104

Hom.:

2489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.324

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0686

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.0736

Gnomad SAS

AF:

0.0877

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0627

Gnomad OTH

AF:

0.111

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

GnomAD4 genome

AF:

0.137

AC:

20831

AN:

152222

Hom.:

2519

Cov.:

AF XY:

0.135

AC XY:

10041

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.325

AC:

13492

AN:

41496

American (AMR)

AF:

0.0685

AC:

1049

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

425

AN:

3468

East Asian (EAS)

AF:

0.0736

AC:

381

AN:

5180

South Asian (SAS)

AF:

0.0861

AC:

415

AN:

4818

European-Finnish (FIN)

AF:

0.0477

AC:

506

AN:

10614

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0627

AC:

4266

AN:

68024

Other (OTH)

AF:

0.111

AC:

235

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

811

1623

2434

3246

4057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0896

Hom.:

1131

Bravo

AF:

0.148

Asia WGS

AF:

0.105

AC:

367

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.93

(source)

DANN

Benign

0.46

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over