rs2682405

chr3-158276049-G-T

Variant summary

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

The NM_001271838.2(RSRC1):c.495-21990G>T variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.409 in 845,602 control chromosomes in the GnomAD database, including 75,339 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 0.48 (17791 hom., cov: 32)
  • Exomes 𝑓: 0.39 (57548 hom.)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.25

Genes affected

RSRC1 (HGNC:24152): (arginine and serine rich coiled-coil 1) This gene encodes a member of the serine and arginine rich-related protein family. The encoded protein is involved in both constitutive and alternative mRNA splicing. This gene may be associated with schizophrenia. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

RPL15P6 (HGNC:36185): (ribosomal protein L15 pseudogene 6)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSRC1	NM_001271838.2	c.495-21990G>T		intron_variant		ENST00000611884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSRC1	ENST00000611884.5	c.495-21990G>T		intron_variant		5	NM_001271838.2	P4
RPL15P6	ENST00000486836.1	n.373C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72298 AN: 151760 Hom.: 17769 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.496

GnomAD4 exome AF: 0.395 AC: 273692 AN: 693726 Hom.: 57548 Cov.: 9 AF XY: 0.391 AC XY: 145772 AN XY: 372952

Gnomad4 AFR exome AF: 0.531

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.476 AC: 72367 AN: 151876 Hom.: 17791 Cov.: 32 AF XY: 0.479 AC XY: 35548 AN XY: 74212

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.494

Alfa AF: 0.433 Hom.: 15066

Bravo AF: 0.479

Asia WGS AF: 0.442 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	2.5
Dann	Benign	0.71

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: rs2682405; hg19: chr3-157993838; COSMIC: COSV55829781;