rs12396

Positions:

• chr15-52121119-G-C
• chr15-52121119-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016194.4(GNB5):​c.*1638C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,074 control chromosomes in the GnomAD database, including 19,263 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 0.45 (19257 hom., cov: 31)
  • Exomes 𝑓: 0.65 (6 hom.)
• Consequence: GNB5 NM_016194.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

Genes affected

GNB5 (HGNC:4401): (G protein subunit beta 5) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. Alternatively spliced transcript variants encoding different isoforms exist. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB5	NM_016194.4	c.*1638C>G		3_prime_UTR_variant	13/13	ENST00000261837.12
GNB5	NM_001379343.1	c.*1638C>G		3_prime_UTR_variant	11/11
GNB5	NM_006578.4	c.*1638C>G		3_prime_UTR_variant	11/11
GNB5	XM_011521162.4	c.*1638C>G		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB5	ENST00000261837.12	c.*1638C>G		3_prime_UTR_variant	13/13	5	NM_016194.4	P3
GNB5	ENST00000396335.8	c.*1638C>G		3_prime_UTR_variant	9/9	1
	ENST00000559825.1	n.396-534G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68533 AN: 151932 Hom.: 19262 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.650 AC: 13 AN: 20 Hom.: 6 Cov.: 0 AF XY: 0.563 AC XY: 9 AN XY: 16

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.722

GnomAD4 genome AF: 0.451 AC: 68520 AN: 152054 Hom.: 19257 Cov.: 31 AF XY: 0.446 AC XY: 33162 AN XY: 74322

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.0155

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.483

Alfa AF: 0.353 Hom.: 938

Bravo AF: 0.422

Asia WGS AF: 0.166 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs12396; hg19: chr15-52413316;