rs12396

Variant names:

• chr15-52121119-G-C
• rs12396
• NM_016194.4:c.*1638C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

GNB5 Gene-Disease associations (from GenCC):

• gnb5-related intellectual disability-cardiac arrhythmia syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• language delay and attention deficit-hyperactivity disorder/cognitive impairment with or without cardiac arrhythmia

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000259327 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GNB5	NM_016194.4	c.*1638C>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000261837.12	NP_057278.2
GNB5	NM_006578.4	c.*1638C>G		3_prime_UTR_variant	Exon 11 of 11		NP_006569.1
GNB5	NM_001379343.1	c.*1638C>G		3_prime_UTR_variant	Exon 11 of 11		NP_001366272.1
GNB5	XM_011521162.4	c.*1638C>G		3_prime_UTR_variant	Exon 11 of 11		XP_011519464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB5	ENST00000261837.12	c.*1638C>G		3_prime_UTR_variant	Exon 13 of 13	5	NM_016194.4	ENSP00000261837.7
GNB5	ENST00000396335.8	c.*1638C>G		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000379626.4
ENSG00000259327	ENST00000559825.1	n.396-534G>C		intron_variant	Intron 1 of 1	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.722 AC: 13 AN: 18

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.160 AC: 6633 AN: 41494

American (AMR) AF: 0.424 AC: 6477 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2389 AN: 3466

East Asian (EAS) AF: 0.0155 AC: 80 AN: 5176

South Asian (SAS) AF: 0.361 AC: 1740 AN: 4826

European-Finnish (FIN) AF: 0.607 AC: 6419 AN: 10576

Middle Eastern (MID) AF: 0.634 AC: 184 AN: 290

European-Non Finnish (NFE) AF: 0.634 AC: 43048 AN: 67932

Other (OTH) AF: 0.483 AC: 1021 AN: 2112

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
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12396; hg19: chr15-52413316;