Variant 1-109603304-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_001377295.2(GNAT2):c.*50G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,020,898 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 11 hom. )

Consequence

GNAT2
NM_001377295.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0300

Variant links:

Genes affected

GNAT2 (HGNC:4394): (G protein subunit alpha transducin 2) Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in cones. [provided by RefSeq, Jul 2008]

GNAT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00301 (458/152200) while in subpopulation NFE AF= 0.0055 (374/68012). AF 95% confidence interval is 0.00504. There are 0 homozygotes in gnomad4. There are 198 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GNAT2	NM_001377295.2 linkuse as main transcript	c.*50G>C	3_prime_UTR_variant	9/9	ENST00000679935.1
GNAT2	NM_001379232.1 linkuse as main transcript	c.*50G>C	3_prime_UTR_variant	9/9
GNAT2	NM_005272.5 linkuse as main transcript	c.*50G>C	3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAT2	ENST00000679935.1 linkuse as main transcript	c.*50G>C		3_prime_UTR_variant	9/9		NM_001377295.2	P1
GNAT2	ENST00000351050.8 linkuse as main transcript	c.*50G>C		3_prime_UTR_variant	8/8	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00301

AC:

458

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00550

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00285

AC:

688

AN:

241000

Hom.:

AF XY:

0.00285

AC XY:

372

AN XY:

130350

show subpopulations

Gnomad AFR exome

AF:

0.000769

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.000709

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000505

Gnomad FIN exome

AF:

0.000946

Gnomad NFE exome

AF:

0.00541

Gnomad OTH exome

AF:

0.00236

GnomAD4 exome

AF:

0.00433

AC:

3759

AN:

868698

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

1874

AN XY:

455976

show subpopulations

Gnomad4 AFR exome

AF:

0.000996

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.000448

Gnomad4 EAS exome

AF:

0.0000271

Gnomad4 SAS exome

AF:

0.000461

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00592

Gnomad4 OTH exome

AF:

0.00433

GnomAD4 genome

AF:

0.00301

AC:

458

AN:

152200

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00550

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00308

Hom.:

Bravo

AF:

0.00308

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Achromatopsia 4

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.1

DANN

Benign

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over