Genetic Variant RSRC1:c.531+4514A>G (chr3-158302589-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001271838.2(RSRC1):c.531+4514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 128,450 control chromosomes in the GnomAD database, including 13,101 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 0.44 ( 13101 hom., cov: 18)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

RSRC1
NM_001271838.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.136

Publications

7 publications found

Variant links:

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

RSRC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2 link	c.531+4514A>G		intron_variant	Intron 5 of 9	ENST00000611884.5	NP_001258767.1	Q96IZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5 link	c.531+4514A>G		intron_variant	Intron 5 of 9	5	NM_001271838.2	ENSP00000481697.1		Q96IZ7-1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

56235

AN:

128380

Hom.:

13092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.668

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.457

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.438

AC:

56265

AN:

128438

Hom.:

13101

Cov.:

AF XY:

0.432

AC XY:

26125

AN XY:

60504

show subpopulations

African (AFR)

AF:

0.522

AC:

17356

AN:

33272

American (AMR)

AF:

0.388

AC:

4632

AN:

11946

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

1553

AN:

3318

East Asian (EAS)

AF:

0.613

AC:

2539

AN:

4140

South Asian (SAS)

AF:

0.262

AC:

1086

AN:

4148

European-Finnish (FIN)

AF:

0.341

AC:

1670

AN:

4900

Middle Eastern (MID)

AF:

0.275

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.407

AC:

26005

AN:

63894

Other (OTH)

AF:

0.456

AC:

804

AN:

1764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

1174

2348

3522

4696

5870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.444

Hom.:

2418

Bravo

AF:

0.479

Asia WGS

AF:

0.425

AC:

1454

AN:

3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.3

(source)

DANN

Benign

0.84

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over