7-80147112-C-T

Variant names:

• chr7-80147112-C-T
• rs2523189
• NM_002069.6:c.118+11834C>T

Variant summary

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

The NM_002069.6(GNAI1):​c.118+11834C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,874 control chromosomes in the GnomAD database, including 6,504 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 0.26 (6504 hom., cov: 31)
• Consequence: GNAI1 NM_002069.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.14
• Publications: 6 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 (AMR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNAI1	NM_002069.6	c.118+11834C>T		intron_variant	Intron 1 of 7	ENST00000649796.2	NP_002060.4
GNAI1	NM_001256414.2	c.-39+11040C>T		intron_variant	Intron 1 of 7		NP_001243343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNAI1	ENST00000649796.2	c.118+11834C>T		intron_variant	Intron 1 of 7		NM_002069.6	ENSP00000497260.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40172 AN: 151754 Hom.: 6498 Cov.: 31

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.265 AC: 40185 AN: 151874 Hom.: 6504 Cov.: 31 AF XY: 0.268 AC XY: 19923 AN XY: 74230

African (AFR) AF: 0.0739 AC: 3064 AN: 41454

American (AMR) AF: 0.340 AC: 5188 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1336 AN: 5128

South Asian (SAS) AF: 0.277 AC: 1330 AN: 4808

European-Finnish (FIN) AF: 0.422 AC: 4437 AN: 10506

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22532 AN: 67944

Other (OTH) AF: 0.300 AC: 632 AN: 2104

Alfa AF: 0.295 Hom.: 14187

Bravo AF: 0.250

Asia WGS AF: 0.253 AC: 881 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	0.028
DANN	Benign	0.60
PhyloP100		-4.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2523189; hg19: chr7-79776428;