chr1-163172378-A-G

Variant names:

• chr1-163172378-A-G
• rs10917690
• NM_003617.4:c.45-4010T>C

Variant summary

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

The NM_003617.4(RGS5):​c.45-4010T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,162 control chromosomes in the GnomAD database, including 6,174 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 0.26 (6174 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657
• Publications: 11 publications found

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

RGS5-AS1 (HGNC:40504): (RGS5 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003617.4. 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
	RGS5	NM_003617.4	MANE Select	c.45-4010T>C		intron	N/A	NP_003608.1
	RGS5	NM_001414472.1		c.66-4010T>C		intron	N/A	NP_001401401.1
	RGS5	NM_001414473.1		c.66-4010T>C		intron	N/A	NP_001401402.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS5	ENST00000313961.10	TSL:1 MANE Select	c.45-4010T>C		intron	N/A	ENSP00000319308.5
	RGS5	ENST00000527988.1	TSL:1	c.-107-19662T>C		intron	N/A	ENSP00000432313.1
	RGS5	ENST00000367903.7	TSL:3	c.104+180T>C		intron	N/A	ENSP00000356879.3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40229 AN: 152044 Hom.: 6170 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.264 AC: 40235 AN: 152162 Hom.: 6174 Cov.: 32 AF XY: 0.274 AC XY: 20356 AN XY: 74370

African (AFR) AF: 0.111 AC: 4596 AN: 41556

American (AMR) AF: 0.315 AC: 4814 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3470

East Asian (EAS) AF: 0.449 AC: 2319 AN: 5160

South Asian (SAS) AF: 0.364 AC: 1754 AN: 4824

European-Finnish (FIN) AF: 0.408 AC: 4316 AN: 10572

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20614 AN: 67980

Other (OTH) AF: 0.279 AC: 589 AN: 2112

Alfa AF: 0.282 Hom.: 8304

Bravo AF: 0.249

Asia WGS AF: 0.361 AC: 1256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		0.66
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: rs10917690; hg19: chr1-163142168; COSMIC: COSV58354419;