Genetic Variant RSRC1:c.653-1923G>A (chr3-158535169-G-A) – 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.653-1923G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,010 control chromosomes in the GnomAD database, including 16,843 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 0.47 ( 16843 hom., cov: 32)

Consequence

RSRC1
NM_001271838.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0920

Publications

12 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, 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=-1.0).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSRC1	NM_001271838.2	MANE Select	c.653-1923G>A	intron	N/A	NP_001258767.1	Q96IZ7-1
RSRC1	NM_016625.4		c.653-1923G>A	intron	N/A	NP_057709.2
RSRC1	NM_001271834.2		c.479-1923G>A	intron	N/A	NP_001258763.1	Q96IZ7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSRC1	ENST00000611884.5	TSL:5 MANE Select	c.653-1923G>A	intron	N/A	ENSP00000481697.1	Q96IZ7-1
RSRC1	ENST00000295930.7	TSL:1	c.653-1923G>A	intron	N/A	ENSP00000295930.3	Q96IZ7-1
RSRC1	ENST00000312179.10	TSL:1	c.479-1923G>A	intron	N/A	ENSP00000308671.6	Q96IZ7-2

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

70997

AN:

150892

Hom.:

16831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.478

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.552

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.449

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

GnomAD4 genome

AF:

0.471

AC:

71059

AN:

151010

Hom.:

16843

Cov.:

AF XY:

0.471

AC XY:

34732

AN XY:

73758

show subpopulations

African (AFR)

AF:

0.484

AC:

20002

AN:

41336

American (AMR)

AF:

0.478

AC:

7223

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

1481

AN:

3450

East Asian (EAS)

AF:

0.243

AC:

1247

AN:

5142

South Asian (SAS)

AF:

0.533

AC:

2573

AN:

4824

European-Finnish (FIN)

AF:

0.470

AC:

4938

AN:

10502

Middle Eastern (MID)

AF:

0.542

AC:

156

AN:

288

European-Non Finnish (NFE)

AF:

0.477

AC:

32125

AN:

67342

Other (OTH)

AF:

0.453

AC:

946

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1939

3877

5816

7754

9693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<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:

0.481

Hom.:

9165

Bravo

AF:

0.465

Asia WGS

AF:

0.440

AC:

1508

AN:

3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

7.7

(source)

DANN

Benign

0.29

PhyloP100

0.092

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over