chr7-80011397-A-G

Variant names:

• chr7-80011397-A-G
• rs7805663
• ENST00000649225.1:c.-337+54331A>G

Variant summary

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

The ENST00000649225.1(GNAI1):​c.-337+54331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,150 control chromosomes in the GnomAD database, including 1,692 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 (1692 hom., cov: 32)
• Consequence: GNAI1 ENST00000649225.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• 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=-0.94).
• 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+54331A>G		intron_variant	Intron 3 of 12			ENSP00000496829.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22232 AN: 152032 Hom.: 1688 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0941

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.0755

Gnomad FIN AF: 0.157

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: 0.146 AC: 22250 AN: 152150 Hom.: 1692 Cov.: 32 AF XY: 0.145 AC XY: 10785 AN XY: 74370

African (AFR) AF: 0.138 AC: 5712 AN: 41518

American (AMR) AF: 0.114 AC: 1742 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0941 AC: 326 AN: 3466

East Asian (EAS) AF: 0.156 AC: 811 AN: 5184

South Asian (SAS) AF: 0.0756 AC: 364 AN: 4816

European-Finnish (FIN) AF: 0.157 AC: 1666 AN: 10592

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

European-Non Finnish (NFE) AF: 0.164 AC: 11177 AN: 67982

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.155 Hom.: 1008

Bravo AF: 0.142

Asia WGS AF: 0.113 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.56
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs7805663; hg19: chr7-79640713;