ENST00000718285.1:n.672+8566G>C

Variant names:

• chr20-58833371-C-G
• rs965808
• ENST00000718285.1:n.672+8566G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000718285.1(GNAS-AS1):​n.672+8566G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: GNAS-AS1 ENST00000718285.1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000718285.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAS-AS1	NR_185847.1	MANE Select	n.672+8566G>C		intron	N/A
	GNAS-AS1	NR_190185.1		n.1970G>C		non_coding_transcript_exon	Exon 5 of 5
	GNAS-AS1	NR_002785.3		n.818+8566G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAS-AS1	ENST00000718285.1	MANE Select	n.672+8566G>C		intron	N/A
	GNAS-AS1	ENST00000424094.6	TSL:1	n.819+8566G>C		intron	N/A
	GNAS-AS1	ENST00000443966.2	TSL:5	n.2120+5354G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 128707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.44
DANN	Benign	0.17
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;