chr3-158149846-C-A

Variant names:

• chr3-158149846-C-A
• rs4271876
• NM_001271838.2:c.320+25855C>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.320+25855C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,932 control chromosomes in the GnomAD database, including 26,968 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 0.59 (26968 hom., cov: 31)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 3 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.320+25855C>A		intron_variant	Intron 3 of 9	ENST00000611884.5	NP_001258767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5	c.320+25855C>A		intron_variant	Intron 3 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90019 AN: 151816 Hom.: 26946 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.593 AC: 90088 AN: 151932 Hom.: 26968 Cov.: 31 AF XY: 0.597 AC XY: 44305 AN XY: 74254

African (AFR) AF: 0.603 AC: 24965 AN: 41428

American (AMR) AF: 0.613 AC: 9360 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2224 AN: 3466

East Asian (EAS) AF: 0.706 AC: 3645 AN: 5160

South Asian (SAS) AF: 0.473 AC: 2278 AN: 4814

European-Finnish (FIN) AF: 0.646 AC: 6819 AN: 10554

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.568 AC: 38616 AN: 67936

Other (OTH) AF: 0.622 AC: 1309 AN: 2106

Alfa AF: 0.577 Hom.: 8795

Bravo AF: 0.596

Asia WGS AF: 0.597 AC: 2077 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.85
PhyloP100		0.23
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: rs4271876; hg19: chr3-157867635;