7-69598914-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015570.4(AUTS2):c.-740T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 153,740 control chromosomes in the GnomAD database, including 5,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5600 hom., cov: 30)
  • Exomes 𝑓: 0.23 (68 hom.)
• Consequence: AUTS2 NM_015570.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 7-69598914-T-G is Benign according to our data. Variant chr7-69598914-T-G is described in ClinVar as [Benign]. Clinvar id is 1226087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AUTS2	NM_015570.4	c.-740T>G		5_prime_UTR_variant	1/19	ENST00000342771.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AUTS2	ENST00000342771.10	c.-740T>G		5_prime_UTR_variant	1/19	1	NM_015570.4	P4
AUTS2	ENST00000644939.1	c.-740T>G		5_prime_UTR_variant	1/19			A1
AUTS2	ENST00000406775.6			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38371 AN: 151680 Hom.: 5597 Cov.: 30

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.228 AC: 443 AN: 1942 Hom.: 68 Cov.: 0 AF XY: 0.225 AC XY: 338 AN XY: 1502

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.253 AC: 38398 AN: 151798 Hom.: 5600 Cov.: 30 AF XY: 0.255 AC XY: 18901 AN XY: 74176

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.228

Alfa AF: 0.218 Hom.: 744

Bravo AF: 0.262

Asia WGS AF: 0.436 AC: 1514 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK:

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

Cadd

Benign

4.2

Dann

Benign

0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73437201; hg19: chr7-69063900;