chr7-69599651-A-G

Position:

• chr7-69599651-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015570.4(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 NM_015570.4 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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
AUTS2	NM_015570.4	c.-3A>G		5_prime_UTR_variant	1/19	ENST00000342771.10	NP_056385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AUTS2	ENST00000342771.10	c.-3A>G		5_prime_UTR_variant	1/19	1	NM_015570.4	ENSP00000344087	P4
AUTS2	ENST00000403018.3	c.-3A>G		5_prime_UTR_variant	1/5	1		ENSP00000385572
AUTS2	ENST00000406775.6	c.-3A>G		5_prime_UTR_variant	1/18	1		ENSP00000385263
AUTS2	ENST00000644939.1	c.-3A>G		5_prime_UTR_variant	1/19			ENSP00000496726	A1

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

GnomAD3 exomes AF: 0.0568 AC: 497 AN: 8750 Hom.: 13 AF XY: 0.0576 AC XY: 263 AN XY: 4564

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 SAS exome AF: 0.0645

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

Gnomad4 AMR exome AF: 0.0766

Gnomad4 ASJ exome AF: 0.0827

Gnomad4 EAS exome AF: 0.0552

Gnomad4 SAS exome AF: 0.0799

Gnomad4 FIN exome AF: 0.0575

Gnomad4 NFE exome AF: 0.0755

Gnomad4 OTH exome AF: 0.0904

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

Gnomad4 AMR AF: 0.0760

Gnomad4 ASJ AF: 0.0820

Gnomad4 EAS AF: 0.0779

Gnomad4 SAS AF: 0.0843

Gnomad4 FIN AF: 0.0616

Gnomad4 NFE AF: 0.0757

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0843 Hom.: 572

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.83

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;