1-84499940-C-T

Variant names:

• chr1-84499940-C-T
• rs56212819
• NM_005274.3:c.*20-1392G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005274.3(GNG5):​c.*20-1392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,102 control chromosomes in the GnomAD database, including 2,442 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 0.18 (2442 hom., cov: 32)
• Consequence: GNG5 NM_005274.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 7 publications found

Genes affected

GNG5 (HGNC:4408): (G protein subunit gamma 5) G proteins are trimeric (alpha-beta-gamma) membrane-associated proteins that regulate flow of information from cell surface receptors to a variety of internal metabolic effectors. Interaction of a G protein with its activated receptor promotes exchange of GTP for GDP that is bound to the alpha subunit. The alpha-GTP complex dissociates from the beta-gamma heterodimer so that the subunits, in turn, may interact with and regulate effector molecules (Gilman, 1987 [PubMed 3113327]; summary by Ahmad et al., 1995) [PubMed 7606925].[supplied by OMIM, Nov 2010]

ENSG00000285851 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG5	NM_005274.3	c.*20-1392G>A		intron_variant	Intron 3 of 3	ENST00000370645.9	NP_005265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG5	ENST00000370645.9	c.*20-1392G>A		intron_variant	Intron 3 of 3	2	NM_005274.3	ENSP00000359679.4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26755 AN: 151982 Hom.: 2437 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.176 AC: 26757 AN: 152102 Hom.: 2442 Cov.: 32 AF XY: 0.179 AC XY: 13283 AN XY: 74354

African (AFR) AF: 0.174 AC: 7204 AN: 41486

American (AMR) AF: 0.216 AC: 3303 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3468

East Asian (EAS) AF: 0.175 AC: 904 AN: 5174

South Asian (SAS) AF: 0.308 AC: 1484 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1562 AN: 10580

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11120 AN: 67996

Other (OTH) AF: 0.160 AC: 336 AN: 2106

Alfa AF: 0.158 Hom.: 282

Bravo AF: 0.177

Asia WGS AF: 0.211 AC: 732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.70
PhyloP100		-0.47
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: rs56212819; hg19: chr1-84965623;