rs4542974

Positions:

• chr3-158127628-T-C
• chr3-158127628-T-G

Variant summary

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

The NM_001271838.2(RSRC1):​c.320+3637T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,046 control chromosomes in the GnomAD database, including 1,396 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 0.12 (1396 hom., cov: 31)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSRC1	NM_001271838.2	c.320+3637T>C		intron_variant		ENST00000611884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSRC1	ENST00000611884.5	c.320+3637T>C		intron_variant		5	NM_001271838.2	P4

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18472 AN: 151928 Hom.: 1394 Cov.: 31

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.122 AC: 18477 AN: 152046 Hom.: 1396 Cov.: 31 AF XY: 0.122 AC XY: 9107 AN XY: 74366

Gnomad4 AFR AF: 0.0370

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0858

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.137

Alfa AF: 0.152 Hom.: 2473

Bravo AF: 0.121

Asia WGS AF: 0.166 AC: 578 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.73

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: rs4542974; hg19: chr3-157845417;