NM_001271838.2:c.-2-2827T>C

Variant names:

• chr3-158119276-T-C
• rs6803630
• NM_001271838.2:c.-2-2827T>C

Variant summary

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

The NM_001271838.2(RSRC1):​c.-2-2827T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,074 control chromosomes in the GnomAD database, including 34,794 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 0.67 (34794 hom., cov: 32)
• Consequence: RSRC1 NM_001271838.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 5 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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRC1	NM_001271838.2	MANE Select	c.-2-2827T>C		intron	N/A	NP_001258767.1
	RSRC1	NM_016625.4		c.-2-2827T>C		intron	N/A	NP_057709.2
	RSRC1	NM_001271834.2		c.-2-2827T>C		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.-2-2827T>C		intron	N/A	ENSP00000481697.1
	RSRC1	ENST00000295930.7	TSL:1	c.-2-2827T>C		intron	N/A	ENSP00000295930.3
	RSRC1	ENST00000312179.10	TSL:1	c.-2-2827T>C		intron	N/A	ENSP00000308671.6

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102409 AN: 151956 Hom.: 34763 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.674 AC: 102492 AN: 152074 Hom.: 34794 Cov.: 32 AF XY: 0.677 AC XY: 50316 AN XY: 74326

African (AFR) AF: 0.703 AC: 29168 AN: 41486

American (AMR) AF: 0.692 AC: 10581 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2587 AN: 3470

East Asian (EAS) AF: 0.828 AC: 4282 AN: 5174

South Asian (SAS) AF: 0.603 AC: 2903 AN: 4816

European-Finnish (FIN) AF: 0.684 AC: 7213 AN: 10544

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43392 AN: 67990

Other (OTH) AF: 0.691 AC: 1457 AN: 2108

Alfa AF: 0.665 Hom.: 5232

Bravo AF: 0.680

Asia WGS AF: 0.724 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		1.9
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: rs6803630; hg19: chr3-157837065;