chr20-58833371-C-A

Variant names:

• chr20-58833371-C-A
• rs965808
• ENST00000424094.6:n.819+8566G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000424094.6(GNAS-AS1):​n.819+8566G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,086 control chromosomes in the GnomAD database, including 42,610 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (42610 hom., cov: 31)
• Consequence: GNAS-AS1 ENST00000424094.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 24 publications found

Genes affected

GNAS-AS1 (HGNC:24872): (GNAS antisense RNA 1) This gene produces a paternally-imprinted antisense RNA transcript that helps regulate the GNAS complex locus, which encodes the alpha subunit of the stimulatory G protein. Defects in this gene are a cause of pseudohypoparathyroidism type Ib.[provided by RefSeq, Jun 2010]

GNAS-AS1 Gene-Disease associations (from GenCC):

• pseudohypoparathyroidism type 1B

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000293655 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAS-AS1	NR_190185.1	n.1970G>T		non_coding_transcript_exon_variant	Exon 5 of 5
GNAS-AS1	NR_002785.3	n.818+8566G>T		intron_variant	Intron 4 of 4
GNAS-AS1	NR_185847.1	n.672+8566G>T		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAS-AS1	ENST00000424094.6	n.819+8566G>T		intron_variant	Intron 4 of 4	1
GNAS-AS1	ENST00000443966.2	n.2120+5354G>T		intron_variant	Intron 1 of 1	5
GNAS-AS1	ENST00000598163.1	n.389-7234G>T		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113261 AN: 151968 Hom.: 42572 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.745 AC: 113343 AN: 152086 Hom.: 42610 Cov.: 31 AF XY: 0.746 AC XY: 55458 AN XY: 74334

African (AFR) AF: 0.682 AC: 28273 AN: 41454

American (AMR) AF: 0.712 AC: 10886 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3470

East Asian (EAS) AF: 0.803 AC: 4153 AN: 5174

South Asian (SAS) AF: 0.763 AC: 3683 AN: 4824

European-Finnish (FIN) AF: 0.826 AC: 8730 AN: 10572

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52713 AN: 67982

Other (OTH) AF: 0.735 AC: 1554 AN: 2114

Alfa AF: 0.758 Hom.: 128707

Bravo AF: 0.735

Asia WGS AF: 0.757 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.54
PhyloP100		-0.60

Splicing

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

Other links and lift over

dbSNP: rs965808; hg19: chr20-57408426;