dbSNP rs6505162: NSRP1:c.20+302A>C (chr17-30117165-A-C) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_032141.4(NSRP1):c.20+302A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 708,838 control chromosomes in the GnomAD database, including 84,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14884 hom., cov: 31)

Exomes 𝑓: 0.49 ( 69874 hom. )

Consequence

NSRP1
NM_032141.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.939

Variant links:

Genes affected

NSRP1 (HGNC:25305): (nuclear speckle splicing regulatory protein 1) Enables mRNA binding activity. Involved in developmental process and regulation of alternative mRNA splicing, via spliceosome. Located in nuclear speck. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

NSRP1 links:

MIR423 (HGNC:31880): (microRNA 423) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR423 links:

hsa-mir-423 (HGNC:):

hsa-mir-423 links:

MIR3184 (HGNC:38182): (microRNA 3184) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3184 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 17-30117165-A-C is Benign according to our data. Variant chr17-30117165-A-C is described in ClinVar as [Benign]. Clinvar id is 1221211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSRP1	NM_032141.4 link	c.20+302A>C		intron_variant	Intron 1 of 6	ENST00000247026.10	NP_115517.1	Q9H0G5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSRP1	ENST00000247026.10 link	c.20+302A>C		intron_variant	Intron 1 of 6	1	NM_032141.4	ENSP00000247026.5		Q9H0G5

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64399

AN:

151734

Hom.:

14886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.545

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.500

AC:

80035

AN:

159944

Hom.:

20940

AF XY:

0.504

AC XY:

43008

AN XY:

85382

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.569

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.792

Gnomad SAS exome

AF:

0.538

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.504

GnomAD4 exome

AF:

0.490

AC:

272803

AN:

556986

Hom.:

69874

Cov.:

AF XY:

0.493

AC XY:

148252

AN XY:

300794

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.556

Gnomad4 EAS exome

AF:

0.801

Gnomad4 SAS exome

AF:

0.543

Gnomad4 FIN exome

AF:

0.435

Gnomad4 NFE exome

AF:

0.455

Gnomad4 OTH exome

AF:

0.479

GnomAD4 genome

AF:

0.424

AC:

64399

AN:

151852

Hom.:

14884

Cov.:

AF XY:

0.432

AC XY:

32082

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.261

Gnomad4 AMR

AF:

0.519

Gnomad4 ASJ

AF:

0.569

Gnomad4 EAS

AF:

0.808

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.430

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.455

Hom.:

16721

Bravo

AF:

0.427

Asia WGS

AF:

0.589

AC:

2049

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22593246, 19950226) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over