rs6946969

chr7-70746041-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015570.4(AUTS2):c.743-16829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,154 control chromosomes in the GnomAD database, including 21,021 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 0.49 (21021 hom., cov: 33)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

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]

LOC105375347 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.743-16829G>A		intron_variant		ENST00000342771.10
LOC105375347	XR_927653.4	n.6044G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.743-16829G>A		intron_variant		1	NM_015570.4	P4

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73904 AN: 152036 Hom.: 20957 Cov.: 33

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.487 AC: 74035 AN: 152154 Hom.: 21021 Cov.: 33 AF XY: 0.484 AC XY: 36011 AN XY: 74392

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.479

Alfa AF: 0.428 Hom.: 4051

Bravo AF: 0.518

Asia WGS AF: 0.612 AC: 2126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.0020
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs6946969; hg19: chr7-70211027;