NM_016194.4:c.127-384G>C

Variant names:

• chr15-52180263-C-G
• rs556137433
• NM_016194.4:c.127-384G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016194.4(GNB5):​c.127-384G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 156,672 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0069 (0 hom.)
• Consequence: GNB5 NM_016194.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970
• Publications: 0 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]

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-52180263-C-G is Benign according to our data. Variant chr15-52180263-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1218201.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00805 (1225/152198) while in subpopulation NFE AF = 0.012 (813/67972). AF 95% confidence interval is 0.0113. There are 7 homozygotes in GnomAd4. There are 609 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016194.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB5	NM_016194.4	MANE Select	c.127-384G>C		intron	N/A	NP_057278.2
	CERNA1	NR_102751.1		n.238C>G		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB5	ENST00000261837.12	TSL:5 MANE Select	c.127-384G>C		intron	N/A	ENSP00000261837.7	O14775-1
	CERNA1	ENST00000559779.2	TSL:3	n.265C>G		non_coding_transcript_exon	Exon 1 of 3
	CERNA1	ENST00000560518.2	TSL:2	n.267C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00805 AC: 1225 AN: 152080 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.00693 AC: 31 AN: 4474 Hom.: 0 Cov.: 0 AF XY: 0.00831 AC XY: 18 AN XY: 2166

African (AFR) AF: 0.00 AC: 0 AN: 160

American (AMR) AF: 0.0135 AC: 1 AN: 74

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 104

East Asian (EAS) AF: 0.00 AC: 0 AN: 132

South Asian (SAS) AF: 0.00 AC: 0 AN: 112

European-Finnish (FIN) AF: 0.00847 AC: 2 AN: 236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.00780 AC: 26 AN: 3334

Other (OTH) AF: 0.00649 AC: 2 AN: 308

GnomAD4 genome AF: 0.00805 AC: 1225 AN: 152198 Hom.: 7 Cov.: 33 AF XY: 0.00818 AC XY: 609 AN XY: 74418

African (AFR) AF: 0.00217 AC: 90 AN: 41550

American (AMR) AF: 0.00732 AC: 112 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4824

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 813 AN: 67972

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00343 Hom.: 2

Bravo AF: 0.00674

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.55
PhyloP100		0.097
PromoterAI		-0.067	Neutral
Mutation Taster		=100/0	polymorphism

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: rs556137433; hg19: chr15-52472460;