rs116688317

Variant names:

• chr1-109603304-C-G
• rs116688317
• NM_001377295.2:c.*50G>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0300
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• achromatopsia 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• GNAT2-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377295.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	NM_001377295.2	MANE Select	c.*50G>C		3_prime_UTR	Exon 9 of 9	NP_001364224.1	P19087
	GNAT2	NM_001379232.1		c.*50G>C		3_prime_UTR	Exon 9 of 9	NP_001366161.1	Q5T697
	GNAT2	NM_005272.5		c.*50G>C		3_prime_UTR	Exon 8 of 8	NP_005263.1	P19087

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNAT2	ENST00000679935.1	MANE Select	c.*50G>C		3_prime_UTR	Exon 9 of 9	ENSP00000505083.1	P19087
	GNAT2	ENST00000351050.8	TSL:1	c.*50G>C		3_prime_UTR	Exon 8 of 8	ENSP00000251337.3	P19087
	GNAT2	ENST00000872463.1		c.*50G>C		3_prime_UTR	Exon 9 of 9	ENSP00000542522.1

Frequencies

GnomAD3 genomes AF: 0.00301 AC: 458 AN: 152082 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00285 AC: 688 AN: 241000 AF XY: 0.00285

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 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.: 11 Cov.: 12 AF XY: 0.00411 AC XY: 1874 AN XY: 455976

African (AFR) AF: 0.000996 AC: 22 AN: 22092

American (AMR) AF: 0.00136 AC: 59 AN: 43448

Ashkenazi Jewish (ASJ) AF: 0.000448 AC: 10 AN: 22314

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36888

South Asian (SAS) AF: 0.000461 AC: 34 AN: 73684

European-Finnish (FIN) AF: 0.00112 AC: 59 AN: 52752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3084

European-Non Finnish (NFE) AF: 0.00592 AC: 3398 AN: 573834

Other (OTH) AF: 0.00433 AC: 176 AN: 40602

GnomAD4 genome AF: 0.00301 AC: 458 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.00266 AC XY: 198 AN XY: 74404

African (AFR) AF: 0.00108 AC: 45 AN: 41520

American (AMR) AF: 0.00144 AC: 22 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00550 AC: 374 AN: 68012

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00308 Hom.: 0

Bravo AF: 0.00308

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Achromatopsia 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.53
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism

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: rs116688317; hg19: chr1-110145926;