rs12698828

Variant names:

• chr7-69981608-C-G
• rs12698828
• NM_015570.4:c.522+82110C>G

Variant summary

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

The NM_015570.4(AUTS2):​c.522+82110C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,122 control chromosomes in the GnomAD database, including 2,043 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 0.16 (2043 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 8 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 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.522+82110C>G		intron	N/A	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.522+82110C>G		intron	N/A	NP_001120703.1	Q8WXX7-2
	AUTS2	NM_001127232.3		c.522+82110C>G		intron	N/A	NP_001120704.1	Q8WXX7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.522+82110C>G		intron	N/A	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.522+82110C>G		intron	N/A	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000403018.3	TSL:1	c.522+82110C>G		intron	N/A	ENSP00000385572.2	Q8WXX7-3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24585 AN: 152004 Hom.: 2036 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.162 AC: 24609 AN: 152122 Hom.: 2043 Cov.: 32 AF XY: 0.163 AC XY: 12114 AN XY: 74348

African (AFR) AF: 0.193 AC: 8011 AN: 41496

American (AMR) AF: 0.176 AC: 2691 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3472

East Asian (EAS) AF: 0.0899 AC: 466 AN: 5186

South Asian (SAS) AF: 0.206 AC: 993 AN: 4814

European-Finnish (FIN) AF: 0.127 AC: 1342 AN: 10570

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10068 AN: 67988

Other (OTH) AF: 0.179 AC: 378 AN: 2106

Alfa AF: 0.152 Hom.: 211

Bravo AF: 0.165

Asia WGS AF: 0.162 AC: 563 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.50
PhyloP100		-1.3
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: rs12698828; hg19: chr7-69446594;