rs4542974

Variant names:

• chr3-158127628-T-C
• rs4542974
• NM_001271838.2:c.320+3637T>C

Your query was ambiguous. Multiple possible variants found:

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

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+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
• 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271838.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	NM_001271838.2	MANE Select	c.320+3637T>C		intron	N/A	NP_001258767.1	Q96IZ7-1
	RSRC1	NM_016625.4		c.320+3637T>C		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.320+3637T>C		intron	N/A	NP_001258763.1	Q96IZ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	ENST00000611884.5	TSL:5 MANE Select	c.320+3637T>C		intron	N/A	ENSP00000481697.1	Q96IZ7-1
	RSRC1	ENST00000295930.7	TSL:1	c.320+3637T>C		intron	N/A	ENSP00000295930.3	Q96IZ7-1
	RSRC1	ENST00000312179.10	TSL:1	c.320+3637T>C		intron	N/A	ENSP00000308671.6	Q96IZ7-2

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

African (AFR) AF: 0.0370 AC: 1536 AN: 41536

American (AMR) AF: 0.172 AC: 2631 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3468

East Asian (EAS) AF: 0.0858 AC: 444 AN: 5176

South Asian (SAS) AF: 0.187 AC: 900 AN: 4820

European-Finnish (FIN) AF: 0.122 AC: 1285 AN: 10528

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10543 AN: 67944

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.150 Hom.: 3058

Bravo AF: 0.121

Asia WGS AF: 0.166 AC: 578 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.73
PhyloP100		0.13
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: rs4542974; hg19: chr3-157845417;