rs7624303

Variant names:

• chr3-158133434-A-G
• rs7624303
• NM_001271838.2:c.320+9443A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001271838.2(RSRC1):​c.320+9443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,156 control chromosomes in the GnomAD database, including 4,237 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 (4237 hom., cov: 33)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2	c.320+9443A>G		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+9443A>G		intron_variant	Intron 3 of 9	5	NM_001271838.2	ENSP00000481697.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33309 AN: 152038 Hom.: 4241 Cov.: 33

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.219 AC: 33298 AN: 152156 Hom.: 4237 Cov.: 33 AF XY: 0.218 AC XY: 16193 AN XY: 74384

African (AFR) AF: 0.0965 AC: 4009 AN: 41552

American (AMR) AF: 0.242 AC: 3701 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 721 AN: 3472

East Asian (EAS) AF: 0.168 AC: 871 AN: 5176

South Asian (SAS) AF: 0.281 AC: 1357 AN: 4824

European-Finnish (FIN) AF: 0.231 AC: 2438 AN: 10568

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19491 AN: 67966

Other (OTH) AF: 0.222 AC: 470 AN: 2114

Alfa AF: 0.268 Hom.: 9241

Bravo AF: 0.213

Asia WGS AF: 0.203 AC: 704 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.85
PhyloP100		2.9
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: rs7624303; hg19: chr3-157851223;