chr7-69599761-C-G

Variant names:

• chr7-69599761-C-G
• rs1051354561
• NM_015570.4:c.108C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_015570.4(AUTS2):​c.108C>G​(p.Gly36Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 1,377,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: AUTS2 NM_015570.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.402
• Publications: 1 publications found

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]

AUTS2 Gene-Disease associations (from GenCC):

• autism spectrum disorder due to AUTS2 deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 7-69599761-C-G is Benign according to our data. Variant chr7-69599761-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 748288.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.402 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000528 (8/151488) while in subpopulation AFR AF = 0.000194 (8/41330). AF 95% confidence interval is 0.0000959. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015570.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	NM_015570.4	MANE Select	c.108C>G	p.Gly36Gly	synonymous	Exon 1 of 19	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.108C>G	p.Gly36Gly	synonymous	Exon 1 of 18	NP_001120703.1	Q8WXX7-2
	AUTS2	NM_001127232.3		c.108C>G	p.Gly36Gly	synonymous	Exon 1 of 5	NP_001120704.1	Q8WXX7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.108C>G	p.Gly36Gly	synonymous	Exon 1 of 19	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.108C>G	p.Gly36Gly	synonymous	Exon 1 of 18	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000403018.3	TSL:1	c.108C>G	p.Gly36Gly	synonymous	Exon 1 of 5	ENSP00000385572.2	Q8WXX7-3

Frequencies

GnomAD3 genomes AF: 0.0000528 AC: 8 AN: 151488 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.16e-7 AC: 1 AN: 1225852 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 598942

African (AFR) AF: 0.0000412 AC: 1 AN: 24286

American (AMR) AF: 0.00 AC: 0 AN: 11812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17950

East Asian (EAS) AF: 0.00 AC: 0 AN: 27508

South Asian (SAS) AF: 0.00 AC: 0 AN: 49594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3600

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1001340

Other (OTH) AF: 0.00 AC: 0 AN: 49774

GnomAD4 genome AF: 0.0000528 AC: 8 AN: 151488 Hom.: 0 Cov.: 32 AF XY: 0.0000676 AC XY: 5 AN XY: 73998

African (AFR) AF: 0.000194 AC: 8 AN: 41330

American (AMR) AF: 0.00 AC: 0 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67782

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		-0.40
PromoterAI		-0.086	Neutral

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

Other links and lift over

dbSNP: rs1051354561; hg19: chr7-69064747;