rs4680433

Variant names:

• chr3-158419059-G-A
• rs4680433
• NM_001271838.2:c.584-41876G>A

Variant summary

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

The NM_001271838.2(RSRC1):​c.584-41876G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,734 control chromosomes in the GnomAD database, including 20,916 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 0.52 (20916 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 12 publications found

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]

RSRC1 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal recessive 70

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.584-41876G>A		intron_variant	Intron 6 of 9	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.584-41876G>A		intron_variant	Intron 6 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78836 AN: 151616 Hom.: 20895 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.520 AC: 78903 AN: 151734 Hom.: 20916 Cov.: 32 AF XY: 0.518 AC XY: 38365 AN XY: 74130

African (AFR) AF: 0.601 AC: 24908 AN: 41420

American (AMR) AF: 0.520 AC: 7899 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1674 AN: 5122

South Asian (SAS) AF: 0.604 AC: 2913 AN: 4824

European-Finnish (FIN) AF: 0.400 AC: 4208 AN: 10532

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34159 AN: 67856

Other (OTH) AF: 0.496 AC: 1046 AN: 2108

Alfa AF: 0.514 Hom.: 6328

Bravo AF: 0.529

Asia WGS AF: 0.510 AC: 1770 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.51
PhyloP100		-0.47
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: rs4680433; hg19: chr3-158136848;