rs11716327

Variant names:

• chr3-158398126-G-T
• rs11716327
• NM_001271838.2:c.583+43218G>T

Variant summary

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

The NM_001271838.2(RSRC1):​c.583+43218G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,896 control chromosomes in the GnomAD database, including 4,200 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 0.22 (4200 hom., cov: 31)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.583+43218G>T		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.583+43218G>T		intron_variant	Intron 6 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33011 AN: 151778 Hom.: 4202 Cov.: 31

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.217 AC: 33002 AN: 151896 Hom.: 4200 Cov.: 31 AF XY: 0.215 AC XY: 15985 AN XY: 74228

African (AFR) AF: 0.0975 AC: 4042 AN: 41466

American (AMR) AF: 0.243 AC: 3708 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3464

East Asian (EAS) AF: 0.0991 AC: 512 AN: 5166

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4810

European-Finnish (FIN) AF: 0.228 AC: 2409 AN: 10554

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19555 AN: 67878

Other (OTH) AF: 0.218 AC: 461 AN: 2110

Alfa AF: 0.262 Hom.: 10945

Bravo AF: 0.211

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.26
PhyloP100		-0.36
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: rs11716327; hg19: chr3-158115915;