7-69599651-A-G

Variant names:

• chr7-69599651-A-G
• rs3735260
• NM_015570.4:c.-3A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000644939(AUTS2):​c.-3A>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 0.0846 in 1,297,190 control chromosomes in the GnomAD database, including 5,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1768 hom., cov: 32)
  • Exomes 𝑓: 0.079 (4036 hom.)
• Consequence: AUTS2 ENST00000644939 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 7-69599651-A-G is Benign according to our data. Variant chr7-69599651-A-G is described in ClinVar as [Benign]. Clinvar id is 1178068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.-3A>G		5_prime_UTR_variant	Exon 1 of 19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771	c.-3A>G		5_prime_UTR_variant	Exon 1 of 19	1	NM_015570.4	ENSP00000344087.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19102 AN: 151634 Hom.: 1760 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0177

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0820

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.0568 AC: 497 AN: 8750 AF XY: 0.0576

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.0420

Gnomad ASJ exome AF: 0.0694

Gnomad EAS exome AF: 0.0286

Gnomad FIN exome AF: 0.0459

Gnomad NFE exome AF: 0.0666

Gnomad OTH exome AF: 0.0672

GnomAD4 exome AF: 0.0791 AC: 90660 AN: 1145448 Hom.: 4036 Cov.: 32 AF XY: 0.0790 AC XY: 43457 AN XY: 550410

Gnomad4 AFR exome AF: 0.263 AC: 6091 AN: 23138

Gnomad4 AMR exome AF: 0.0766 AC: 678 AN: 8850

Gnomad4 ASJ exome AF: 0.0827 AC: 1243 AN: 15022

Gnomad4 EAS exome AF: 0.0552 AC: 1484 AN: 26900

Gnomad4 SAS exome AF: 0.0799 AC: 2489 AN: 31150

Gnomad4 FIN exome AF: 0.0575 AC: 1854 AN: 32234

Gnomad4 NFE exome AF: 0.0755 AC: 72407 AN: 958832

Gnomad4 Remaining exome AF: 0.0904 AC: 4178 AN: 46240

GnomAD4 genome AF: 0.126 AC: 19136 AN: 151742 Hom.: 1768 Cov.: 32 AF XY: 0.124 AC XY: 9223 AN XY: 74176

Gnomad4 AFR AF: 0.262 AC: 0.261732 AN: 0.261732

Gnomad4 AMR AF: 0.0760 AC: 0.0760429 AN: 0.0760429

Gnomad4 ASJ AF: 0.0820 AC: 0.0820335 AN: 0.0820335

Gnomad4 EAS AF: 0.0779 AC: 0.07794 AN: 0.07794

Gnomad4 SAS AF: 0.0843 AC: 0.0843023 AN: 0.0843023

Gnomad4 FIN AF: 0.0616 AC: 0.0615735 AN: 0.0615735

Gnomad4 NFE AF: 0.0757 AC: 0.0757089 AN: 0.0757089

Gnomad4 OTH AF: 0.107 AC: 0.106565 AN: 0.106565

Alfa AF: 0.0916 Hom.: 915

Bravo AF: 0.134

Asia WGS AF: 0.101 AC: 351 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.83
Mutation Taster		=300/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs3735260; hg19: chr7-69064637;