17-30137456-T-C

Variant names:

• chr17-30137456-T-C
• rs4470197
• NM_032141.4:c.114+19283T>C

Variant summary

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

The NM_032141.4(NSRP1):​c.114+19283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,070 control chromosomes in the GnomAD database, including 19,331 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 0.50 (19331 hom., cov: 32)
• Consequence: NSRP1 NM_032141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with spasticity, seizures, and brain abnormalities

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032141.4. 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
	NSRP1	NM_032141.4	MANE Select	c.114+19283T>C		intron	N/A	NP_115517.1
	NSRP1	NM_001261467.2		c.-49+20593T>C		intron	N/A	NP_001248396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSRP1	ENST00000247026.10	TSL:1 MANE Select	c.114+19283T>C		intron	N/A	ENSP00000247026.5
	NSRP1	ENST00000612959.4	TSL:1	c.-49+20593T>C		intron	N/A	ENSP00000477862.1
	NSRP1	ENST00000394826.8	TSL:1	n.21-19084T>C		intron	N/A	ENSP00000378303.4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75525 AN: 151952 Hom.: 19325 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.497 AC: 75554 AN: 152070 Hom.: 19331 Cov.: 32 AF XY: 0.502 AC XY: 37304 AN XY: 74356

African (AFR) AF: 0.515 AC: 21344 AN: 41474

American (AMR) AF: 0.541 AC: 8261 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1942 AN: 3472

East Asian (EAS) AF: 0.816 AC: 4223 AN: 5174

South Asian (SAS) AF: 0.533 AC: 2573 AN: 4824

European-Finnish (FIN) AF: 0.438 AC: 4632 AN: 10574

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30927 AN: 67966

Other (OTH) AF: 0.509 AC: 1074 AN: 2112

Alfa AF: 0.476 Hom.: 69527

Bravo AF: 0.508

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.46
PhyloP100		-2.1
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: rs4470197; hg19: chr17-28464474; COSMIC: COSV55935231;