rs6949651

chr7-70074154-G-Achr7-70074154-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_015570.4(AUTS2):c.523-43978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,080 control chromosomes in the GnomAD database, including 8,897 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 0.34 (8897 hom., cov: 32)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.523-43978G>A		intron_variant		ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.523-43978G>A		intron_variant		1	NM_015570.4	P4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51283 AN: 151962 Hom.: 8879 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.338 AC: 51347 AN: 152080 Hom.: 8897 Cov.: 32 AF XY: 0.339 AC XY: 25200 AN XY: 74332

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.349

Alfa AF: 0.230 Hom.: 638

Bravo AF: 0.338

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	14
Dann	Benign	0.63

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: rs6949651; hg19: chr7-69539140;