chr1-163070705-G-T

Position:

• chr1-163070705-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367909.11(RGS4):​c.44+1177G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,024 control chromosomes in the GnomAD database, including 21,406 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 0.53 (21406 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RGS4 ENST00000367909.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

Genes affected

RGS4 (HGNC:10000): (regulator of G protein signaling 4) Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain. Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulate signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS4	NM_005613.6	c.44+1177G>T		intron_variant		ENST00000367909.11	NP_005604.1
RGS4	NM_001102445.3	c.335+1177G>T		intron_variant			NP_001095915.1
RGS4	NM_001113381.1	c.44+1177G>T		intron_variant			NP_001106852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS4	ENST00000367909.11	c.44+1177G>T		intron_variant		1	NM_005613.6	ENSP00000356885	P1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79971 AN: 151904 Hom.: 21407 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.523

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.526 AC: 79996 AN: 152024 Hom.: 21406 Cov.: 32 AF XY: 0.525 AC XY: 39026 AN XY: 74324

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.520

Alfa AF: 0.530 Hom.: 5835

Bravo AF: 0.524

Asia WGS AF: 0.421 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.4
DANN	Benign	0.85

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: rs2842030; hg19: chr1-163040495;