rs1043879

chr1-25243590-T-C

Variant summary

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

The NM_020317.5(RSRP1):c.716A>G(p.Glu239Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,613,258 control chromosomes in the GnomAD database, including 47,036 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (3451 hom., cov: 32)
  • Exomes 𝑓: 0.23 (43585 hom.)
• Consequence: RSRP1 NM_020317.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

Genes affected

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004683733).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSRP1	NM_020317.5	c.716A>G	p.Glu239Gly	missense_variant	4/5	ENST00000243189.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSRP1	ENST00000243189.12	c.716A>G	p.Glu239Gly	missense_variant	4/5	1	NM_020317.5	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28438 AN: 152110 Hom.: 3450 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.222

GnomAD3 exomes AF: 0.202 AC: 50877 AN: 251340 Hom.: 6360 AF XY: 0.208 AC XY: 28310 AN XY: 135862

Gnomad AFR exome AF: 0.0445

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.384

Gnomad EAS exome AF: 0.0226

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.234 AC: 341409 AN: 1461030 Hom.: 43585 Cov.: 32 AF XY: 0.233 AC XY: 169387 AN XY: 726846

Gnomad4 AFR exome AF: 0.0432

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.0160

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.187 AC: 28437 AN: 152228 Hom.: 3451 Cov.: 32 AF XY: 0.186 AC XY: 13843 AN XY: 74430

Gnomad4 AFR AF: 0.0504

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.221

Alfa AF: 0.248 Hom.: 10563

Bravo AF: 0.177

TwinsUK AF: 0.261 AC: 968

ALSPAC AF: 0.259 AC: 998

ESP6500AA AF: 0.0538 AC: 237

ESP6500EA AF: 0.268 AC: 2306

ExAC AF: 0.200 AC: 24236

Asia WGS AF: 0.0900 AC: 313 AN: 3476

EpiCase AF: 0.276

EpiControl AF: 0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	15
Dann	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.92	P;P
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.088
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.30	T
Polyphen		0.087	B
Vest4		0.086
MPC		0.21
ClinPred		0.031	T
GERP RS		4.0
Varity_R		0.19
gMVP		0.30

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: rs1043879; hg19: chr1-25570081; COSMIC: COSV54562947; COSMIC: COSV54562947;