rs1018933

Variant names:

• chr7-80117245-C-T
• rs1018933
• ENST00000648663.1:c.-378+5867C>T

Variant summary

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

The ENST00000648663.1(GNAI1):​c.-378+5867C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,186 control chromosomes in the GnomAD database, including 55,287 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 0.85 (55287 hom., cov: 32)
• Consequence: GNAI1 ENST00000648663.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 2 publications found

Genes affected

GNAI1 (HGNC:4384): (G protein subunit alpha i1) Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The alpha subunit binds guanine nucleotide, can hydrolyze GTP, and can interact with other proteins. The protein encoded by this gene represents the alpha subunit of an inhibitory complex. The encoded protein is part of a complex that responds to beta-adrenergic signals by inhibiting adenylate cyclase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GNAI1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Broad Center for Mendelian Genomics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648663.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI1	ENST00000648663.1		c.-378+5867C>T		intron	N/A	ENSP00000497379.1
	GNAI1	ENST00000649225.1		c.-248-16975C>T		intron	N/A	ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129516 AN: 152068 Hom.: 55239 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.852 AC: 129620 AN: 152186 Hom.: 55287 Cov.: 32 AF XY: 0.855 AC XY: 63611 AN XY: 74392

African (AFR) AF: 0.825 AC: 34226 AN: 41508

American (AMR) AF: 0.880 AC: 13445 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3028 AN: 3472

East Asian (EAS) AF: 0.853 AC: 4416 AN: 5176

South Asian (SAS) AF: 0.907 AC: 4374 AN: 4820

European-Finnish (FIN) AF: 0.848 AC: 8983 AN: 10596

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.857 AC: 58280 AN: 68010

Other (OTH) AF: 0.857 AC: 1812 AN: 2114

Alfa AF: 0.859 Hom.: 44489

Bravo AF: 0.850

Asia WGS AF: 0.882 AC: 3067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.72
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs1018933; hg19: chr7-79746561; COSMIC: COSV53898813;