rs6505162

Variant names:

• chr17-30117165-A-C
• rs6505162
• NM_032141.4:c.20+302A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-30117165-A-C
• chr17-30117165-A-G
• chr17-30117165-A-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.939
• Publications: 184 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]

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]

hsa-mir-423 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSRP1	NM_032141.4	MANE Select	c.20+302A>C		intron	N/A	NP_115517.1	Q9H0G5
	NSRP1	NM_001261467.2		c.-49+302A>C		intron	N/A	NP_001248396.1	A0A024QZ33
	MIR423	NR_029945.1		n.87A>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSRP1	ENST00000247026.10	TSL:1 MANE Select	c.20+302A>C		intron	N/A	ENSP00000247026.5	Q9H0G5
	NSRP1	ENST00000612959.4	TSL:1	c.-49+302A>C		intron	N/A	ENSP00000477862.1	A0A024QZ33
	NSRP1	ENST00000394826.8	TSL:1	n.20+302A>C		intron	N/A	ENSP00000378303.4	H7BYM1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64399 AN: 151734 Hom.: 14886 Cov.: 31

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

GnomAD2 exomes AF: 0.500 AC: 80035 AN: 159944 AF XY: 0.504

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 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.: 2 AF XY: 0.493 AC XY: 148252 AN XY: 300794

African (AFR) AF: 0.267 AC: 4052 AN: 15162

American (AMR) AF: 0.562 AC: 18974 AN: 33788

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 10747 AN: 19312

East Asian (EAS) AF: 0.801 AC: 26027 AN: 32490

South Asian (SAS) AF: 0.543 AC: 33690 AN: 62066

European-Finnish (FIN) AF: 0.435 AC: 21322 AN: 48996

Middle Eastern (MID) AF: 0.557 AC: 1534 AN: 2756

European-Non Finnish (NFE) AF: 0.455 AC: 142123 AN: 312492

Other (OTH) AF: 0.479 AC: 14334 AN: 29924

GnomAD4 genome AF: 0.424 AC: 64399 AN: 151852 Hom.: 14884 Cov.: 31 AF XY: 0.432 AC XY: 32082 AN XY: 74178

African (AFR) AF: 0.261 AC: 10796 AN: 41398

American (AMR) AF: 0.519 AC: 7913 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1974 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4167 AN: 5160

South Asian (SAS) AF: 0.553 AC: 2659 AN: 4806

European-Finnish (FIN) AF: 0.430 AC: 4529 AN: 10532

Middle Eastern (MID) AF: 0.524 AC: 152 AN: 290

European-Non Finnish (NFE) AF: 0.454 AC: 30809 AN: 67924

Other (OTH) AF: 0.465 AC: 982 AN: 2112

Alfa AF: 0.449 Hom.: 44252

Bravo AF: 0.427

Asia WGS AF: 0.589 AC: 2049 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.82
PhyloP100		0.94
PromoterAI		0.021	Neutral
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: rs6505162; hg19: chr17-28444183; COSMIC: COSV55936190; COSMIC: COSV55936190;