rs7803811

Variant names:

• chr7-80002140-C-A
• rs7803811
• ENST00000649225.1:c.-337+45074C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-80002140-C-A
• chr7-80002140-C-T

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-337+45074C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,574 control chromosomes in the GnomAD database, including 1,693 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 0.15 (1693 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAI1	ENST00000649225.1	c.-337+45074C>A		intron_variant	Intron 3 of 12			ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22233 AN: 151458 Hom.: 1689 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.147 AC: 22251 AN: 151574 Hom.: 1693 Cov.: 32 AF XY: 0.146 AC XY: 10784 AN XY: 74032

African (AFR) AF: 0.138 AC: 5714 AN: 41342

American (AMR) AF: 0.113 AC: 1717 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3464

East Asian (EAS) AF: 0.156 AC: 803 AN: 5152

South Asian (SAS) AF: 0.0759 AC: 366 AN: 4820

European-Finnish (FIN) AF: 0.159 AC: 1659 AN: 10448

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11134 AN: 67852

Other (OTH) AF: 0.146 AC: 307 AN: 2100

Alfa AF: 0.138 Hom.: 818

Bravo AF: 0.142

Asia WGS AF: 0.112 AC: 386 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.6
DANN	Benign	0.67
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs7803811; hg19: chr7-79631456;