chr1-109548649-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006496.4(GNAI3):​c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,040,390 control chromosomes in the GnomAD database, including 22,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2788 hom., cov: 32)
Exomes 𝑓: 0.20 ( 19407 hom. )

Consequence

GNAI3
NM_006496.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0100
Variant links:
Genes affected
GNAI3 (HGNC:4387): (G protein subunit alpha i3) Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling pathways. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes an alpha subunit and belongs to the G-alpha family. Mutation in this gene, resulting in a gly40-to-arg substitution, is associated with auriculocondylar syndrome, and shown to affect downstream targets in the G protein-coupled endothelin receptor pathway. [provided by RefSeq, Jun 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 1-109548649-C-T is Benign according to our data. Variant chr1-109548649-C-T is described in ClinVar as [Benign]. Clinvar id is 1274531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GNAI3NM_006496.4 linkuse as main transcriptc.-72C>T 5_prime_UTR_variant 1/9 ENST00000369851.7 NP_006487.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GNAI3ENST00000369851.7 linkuse as main transcriptc.-72C>T 5_prime_UTR_variant 1/91 NM_006496.4 ENSP00000358867 P1

Frequencies

GnomAD3 genomes
AF:
0.183
AC:
27809
AN:
152028
Hom.:
2789
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.137
Gnomad AMI
AF:
0.296
Gnomad AMR
AF:
0.161
Gnomad ASJ
AF:
0.231
Gnomad EAS
AF:
0.362
Gnomad SAS
AF:
0.294
Gnomad FIN
AF:
0.209
Gnomad MID
AF:
0.155
Gnomad NFE
AF:
0.186
Gnomad OTH
AF:
0.181
GnomAD4 exome
AF:
0.201
AC:
178615
AN:
888242
Hom.:
19407
Cov.:
12
AF XY:
0.205
AC XY:
93668
AN XY:
457828
show subpopulations
Gnomad4 AFR exome
AF:
0.131
Gnomad4 AMR exome
AF:
0.178
Gnomad4 ASJ exome
AF:
0.234
Gnomad4 EAS exome
AF:
0.343
Gnomad4 SAS exome
AF:
0.287
Gnomad4 FIN exome
AF:
0.199
Gnomad4 NFE exome
AF:
0.186
Gnomad4 OTH exome
AF:
0.204
GnomAD4 genome
AF:
0.183
AC:
27824
AN:
152148
Hom.:
2788
Cov.:
32
AF XY:
0.186
AC XY:
13810
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.137
Gnomad4 AMR
AF:
0.162
Gnomad4 ASJ
AF:
0.231
Gnomad4 EAS
AF:
0.360
Gnomad4 SAS
AF:
0.294
Gnomad4 FIN
AF:
0.209
Gnomad4 NFE
AF:
0.186
Gnomad4 OTH
AF:
0.182
Alfa
AF:
0.182
Hom.:
420
Bravo
AF:
0.176
Asia WGS
AF:
0.296
AC:
1027
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMay 12, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
4.1
DANN
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3737182; hg19: chr1-110091271; COSMIC: COSV63983763; COSMIC: COSV63983763; API