7-80213989-C-T

Variant names:

• chr7-80213989-C-T
• rs2886611
• NM_002069.6:c.874+1120C>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.874+1120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,904 control chromosomes in the GnomAD database, including 7,187 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 0.29 (7187 hom., cov: 31)
• Consequence: GNAI1 NM_002069.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002069.6. 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
	GNAI1	NM_002069.6	MANE Select	c.874+1120C>T		intron	N/A	NP_002060.4
	GNAI1	NM_001256414.2		c.718+1120C>T		intron	N/A	NP_001243343.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAI1	ENST00000649796.2	MANE Select	c.874+1120C>T		intron	N/A	ENSP00000497260.1
	GNAI1	ENST00000351004.8	TSL:1	c.874+1120C>T		intron	N/A	ENSP00000343027.3
	GNAI1	ENST00000647672.1		c.*1097C>T		3_prime_UTR	Exon 4 of 4	ENSP00000497802.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43275 AN: 151786 Hom.: 7182 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.285 AC: 43304 AN: 151904 Hom.: 7187 Cov.: 31 AF XY: 0.282 AC XY: 20923 AN XY: 74252

African (AFR) AF: 0.458 AC: 18948 AN: 41380

American (AMR) AF: 0.231 AC: 3523 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3466

East Asian (EAS) AF: 0.130 AC: 669 AN: 5154

South Asian (SAS) AF: 0.136 AC: 653 AN: 4812

European-Finnish (FIN) AF: 0.215 AC: 2272 AN: 10552

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15752 AN: 67970

Other (OTH) AF: 0.252 AC: 532 AN: 2110

Alfa AF: 0.245 Hom.: 20554

Bravo AF: 0.294

Asia WGS AF: 0.130 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-0.51
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: rs2886611; hg19: chr7-79843305;