rs4680436

Variant names:

• chr3-158441528-G-A
• rs4680436
• NM_001271838.2:c.584-19407G>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.584-19407G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,622 control chromosomes in the GnomAD database, including 20,642 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 (20642 hom., cov: 31)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.584-19407G>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.584-19407G>A		intron_variant	Intron 6 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78225 AN: 151502 Hom.: 20619 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.516 AC: 78296 AN: 151622 Hom.: 20642 Cov.: 31 AF XY: 0.513 AC XY: 38020 AN XY: 74056

African (AFR) AF: 0.600 AC: 24790 AN: 41316

American (AMR) AF: 0.516 AC: 7865 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1619 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1677 AN: 5120

South Asian (SAS) AF: 0.602 AC: 2894 AN: 4804

European-Finnish (FIN) AF: 0.383 AC: 4011 AN: 10478

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

European-Non Finnish (NFE) AF: 0.500 AC: 33964 AN: 67888

Other (OTH) AF: 0.496 AC: 1045 AN: 2106

Alfa AF: 0.518 Hom.: 3518

Bravo AF: 0.526

Asia WGS AF: 0.510 AC: 1771 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.26
PhyloP100		-0.21
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: rs4680436; hg19: chr3-158159317;