15-52191368-A-G

Position:

• chr15-52191368-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016194.4(GNB5):​c.-65T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,228 control chromosomes in the GnomAD database, including 31,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31867 hom., cov: 32)
  • Exomes 𝑓: 0.63 (20 hom.)
• Consequence: GNB5 NM_016194.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.456

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]

CERNA1 (HGNC:52664): (competing endogenous lncRNA 1 for miR-4707-5p and miR-4767)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-52191368-A-G is Benign according to our data. Variant chr15-52191368-A-G is described in ClinVar as [Benign]. Clinvar id is 1244293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB5	NM_016194.4	c.-65T>C		5_prime_UTR_variant	1/13	ENST00000261837.12
CERNA1	NR_102751.1	n.529+10166A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB5	ENST00000261837.12	c.-65T>C		5_prime_UTR_variant	1/13	5	NM_016194.4	P3
CERNA1	ENST00000654724.1	n.527+10166A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95312 AN: 152010 Hom.: 31876 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.630 AC: 63 AN: 100 Hom.: 20 Cov.: 0 AF XY: 0.621 AC XY: 36 AN XY: 58

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.595

GnomAD4 genome AF: 0.627 AC: 95326 AN: 152128 Hom.: 31867 Cov.: 32 AF XY: 0.624 AC XY: 46439 AN XY: 74394

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.616

Alfa AF: 0.713 Hom.: 74947

Bravo AF: 0.591

Asia WGS AF: 0.476 AC: 1656 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.72

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: rs11070883; hg19: chr15-52483565;