rs10486928

Variant names:

• chr7-80149921-T-C
• rs10486928
• NM_002069.6:c.118+14643T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-80149921-T-C
• chr7-80149921-T-G

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+14643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 152,232 control chromosomes in the GnomAD database, including 219 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 0.043 (219 hom., cov: 32)
• Consequence: GNAI1 NM_002069.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 0 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 (AFR) allele frequency at 95% confidence interval = 0.0977 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.118+14643T>C		intron	N/A	NP_002060.4
	GNAI1	NM_001256414.2		c.-39+13849T>C		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.118+14643T>C		intron	N/A	ENSP00000497260.1
	GNAI1	ENST00000351004.8	TSL:1	c.118+14643T>C		intron	N/A	ENSP00000343027.3
	GNAI1	ENST00000442586.2	TSL:4	c.118+14643T>C		intron	N/A	ENSP00000391439.2

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6476 AN: 152114 Hom.: 219 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0483

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

GnomAD4 genome AF: 0.0425 AC: 6476 AN: 152232 Hom.: 219 Cov.: 32 AF XY: 0.0415 AC XY: 3088 AN XY: 74444

African (AFR) AF: 0.100 AC: 4162 AN: 41522

American (AMR) AF: 0.0355 AC: 543 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3464

East Asian (EAS) AF: 0.0639 AC: 331 AN: 5182

South Asian (SAS) AF: 0.0379 AC: 183 AN: 4826

European-Finnish (FIN) AF: 0.00414 AC: 44 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0133 AC: 907 AN: 68010

Other (OTH) AF: 0.0473 AC: 100 AN: 2114

Alfa AF: 0.0254 Hom.: 36

Bravo AF: 0.0484

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		0.026
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: rs10486928; hg19: chr7-79779237;