3-179401348-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_021629.4(GNB4):c.917-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,504,044 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (7 hom.)
• Consequence: GNB4 NM_021629.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

Genes affected

GNB4 (HGNC:20731): (G protein subunit beta 4) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-179401348-C-T is Benign according to our data. Variant chr3-179401348-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194837.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00218 (331/152148) while in subpopulation NFE AF= 0.00234 (159/68006). AF 95% confidence interval is 0.00204. There are 2 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 331 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB4	NM_021629.4	c.917-29G>A		intron_variant		ENST00000232564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB4	ENST00000232564.8	c.917-29G>A		intron_variant		1	NM_021629.4	P1

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 331 AN: 152030 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00223 AC: 537 AN: 240890 Hom.: 2 AF XY: 0.00207 AC XY: 270 AN XY: 130420

Gnomad AFR exome AF: 0.000259

Gnomad AMR exome AF: 0.000621

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.00244

Gnomad OTH exome AF: 0.00226

GnomAD4 exome AF: 0.00209 AC: 2831 AN: 1351896 Hom.: 7 Cov.: 19 AF XY: 0.00203 AC XY: 1379 AN XY: 677902

Gnomad4 AFR exome AF: 0.000194

Gnomad4 AMR exome AF: 0.000585

Gnomad4 ASJ exome AF: 0.0000797

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.00206

Gnomad4 OTH exome AF: 0.00183

GnomAD4 genome AF: 0.00218 AC: 331 AN: 152148 Hom.: 2 Cov.: 32 AF XY: 0.00242 AC XY: 180 AN XY: 74370

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0117

Gnomad4 NFE AF: 0.00234

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00115 Hom.: 0

Bravo AF: 0.00137

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.76
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs186397073; hg19: chr3-179119136;