chr7-70616753-G-GTTT

Variant names:

• chr7-70616753-G-GTTT
• rs67691820
• NM_015570.4:c.691-81800_691-81798dupTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_015570.4(AUTS2):​c.691-81800_691-81798dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0024 (7 hom., cov: 0)
• Consequence: AUTS2 NM_015570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 0 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00237 (311/131270) while in subpopulation EAS AF = 0.0449 (196/4368). AF 95% confidence interval is 0.0397. There are 7 homozygotes in GnomAd4. There are 155 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 311 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.691-81800_691-81798dupTTT		intron	N/A	NP_056385.1	Q8WXX7-1
	AUTS2	NM_001127231.3		c.691-81800_691-81798dupTTT		intron	N/A	NP_001120703.1	Q8WXX7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AUTS2	ENST00000342771.10	TSL:1 MANE Select	c.691-81816_691-81815insTTT		intron	N/A	ENSP00000344087.4	Q8WXX7-1
	AUTS2	ENST00000406775.6	TSL:1	c.691-81816_691-81815insTTT		intron	N/A	ENSP00000385263.2	Q8WXX7-2
	AUTS2	ENST00000644939.1		c.691-81816_691-81815insTTT		intron	N/A	ENSP00000496726.1	A0A2R8Y8C6

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 311 AN: 131288 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00102

Gnomad ASJ AF: 0.000910

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.00380

Gnomad FIN AF: 0.000824

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000271

Gnomad OTH AF: 0.00341

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

GnomAD4 genome AF: 0.00237 AC: 311 AN: 131270 Hom.: 7 Cov.: 0 AF XY: 0.00249 AC XY: 155 AN XY: 62246

African (AFR) AF: 0.00159 AC: 56 AN: 35256

American (AMR) AF: 0.00102 AC: 13 AN: 12738

Ashkenazi Jewish (ASJ) AF: 0.000910 AC: 3 AN: 3296

East Asian (EAS) AF: 0.0449 AC: 196 AN: 4368

South Asian (SAS) AF: 0.00382 AC: 15 AN: 3930

European-Finnish (FIN) AF: 0.000824 AC: 5 AN: 6068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.000271 AC: 17 AN: 62780

Other (OTH) AF: 0.00339 AC: 6 AN: 1768

Alfa AF: 0.00 Hom.: 331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs67691820; hg19: chr7-70081739;