chr5-177371305-G-A

Variant names:

• chr5-177371305-G-A
• rs11746443
• NM_006480.5:c.1337-45G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006480.5(RGS14):​c.1337-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,613,770 control chromosomes in the GnomAD database, including 54,290 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 0.21 (4172 hom., cov: 30)
  • Exomes 𝑓: 0.26 (50118 hom.)
• Consequence: RGS14 NM_006480.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 47 publications found

Genes affected

RGS14 (HGNC:9996): (regulator of G protein signaling 14) This gene encodes a member of the regulator of G-protein signaling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006480.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS14	NM_006480.5	MANE Select	c.1337-45G>A		intron	N/A	NP_006471.2
	RGS14	NM_001366617.1		c.1340-45G>A		intron	N/A	NP_001353546.1
	RGS14	NM_001366618.1		c.1340-45G>A		intron	N/A	NP_001353547.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS14	ENST00000408923.8	TSL:1 MANE Select	c.1337-45G>A		intron	N/A	ENSP00000386229.3
	RGS14	ENST00000511890.1	TSL:1	c.947-45G>A		intron	N/A	ENSP00000422329.1
	RGS14	ENST00000425155.6	TSL:2	n.1444-45G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32486 AN: 151912 Hom.: 4171 Cov.: 30

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.243 AC: 60643 AN: 249472 AF XY: 0.252

Gnomad AFR exome AF: 0.0733

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.258 AC: 377106 AN: 1461740 Hom.: 50118 Cov.: 37 AF XY: 0.260 AC XY: 188846 AN XY: 727186

African (AFR) AF: 0.0716 AC: 2397 AN: 33478

American (AMR) AF: 0.186 AC: 8323 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6982 AN: 26136

East Asian (EAS) AF: 0.205 AC: 8155 AN: 39700

South Asian (SAS) AF: 0.277 AC: 23896 AN: 86254

European-Finnish (FIN) AF: 0.328 AC: 17500 AN: 53398

Middle Eastern (MID) AF: 0.255 AC: 1472 AN: 5768

European-Non Finnish (NFE) AF: 0.264 AC: 293600 AN: 1111888

Other (OTH) AF: 0.245 AC: 14781 AN: 60396

GnomAD4 genome AF: 0.214 AC: 32480 AN: 152030 Hom.: 4172 Cov.: 30 AF XY: 0.216 AC XY: 16029 AN XY: 74288

African (AFR) AF: 0.0805 AC: 3341 AN: 41498

American (AMR) AF: 0.223 AC: 3415 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3466

East Asian (EAS) AF: 0.153 AC: 790 AN: 5170

South Asian (SAS) AF: 0.264 AC: 1270 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3663 AN: 10574

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18459 AN: 67908

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.257 Hom.: 18165

Bravo AF: 0.197

Asia WGS AF: 0.220 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.81
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism (auto)

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: rs11746443; hg19: chr5-176798306; COSMIC: COSV68771153; COSMIC: COSV68771153;