rs1714518

Variant names:

• chr3-158495634-C-T
• rs1714518
• NM_001271838.2:c.652+34631C>T

Variant summary

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

The NM_016625.4(RSRC1):​c.652+34631C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,044 control chromosomes in the GnomAD database, including 16,691 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 0.46 (16691 hom., cov: 32)
• Consequence: RSRC1 NM_016625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	NM_001271838.2	MANE Select	c.652+34631C>T		intron	N/A	NP_001258767.1
	RSRC1	NM_016625.4		c.652+34631C>T		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.478+34631C>T		intron	N/A	NP_001258763.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	ENST00000611884.5	TSL:5 MANE Select	c.652+34631C>T		intron	N/A	ENSP00000481697.1
	RSRC1	ENST00000295930.7	TSL:1	c.652+34631C>T		intron	N/A	ENSP00000295930.3
	RSRC1	ENST00000312179.10	TSL:1	c.478+34631C>T		intron	N/A	ENSP00000308671.6

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70159 AN: 151926 Hom.: 16682 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.462 AC: 70204 AN: 152044 Hom.: 16691 Cov.: 32 AF XY: 0.462 AC XY: 34317 AN XY: 74304

African (AFR) AF: 0.352 AC: 14610 AN: 41488

American (AMR) AF: 0.468 AC: 7160 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1686 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3311 AN: 5162

South Asian (SAS) AF: 0.396 AC: 1904 AN: 4812

European-Finnish (FIN) AF: 0.541 AC: 5701 AN: 10546

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34142 AN: 67974

Other (OTH) AF: 0.477 AC: 1003 AN: 2102

Alfa AF: 0.480 Hom.: 8983

Bravo AF: 0.455

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.44
PhyloP100		0.38
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: rs1714518; hg19: chr3-158213423;