rs1410592

Variant names:

• chr1-179551371-G-A
• rs1410592
• NM_014625.4:c.954C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-179551371-G-A
• chr1-179551371-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014625.4(NPHS2):​c.954C>T​(p.Ala318Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,613,796 control chromosomes in the GnomAD database, including 308,950 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28814 hom., cov: 31)
  • Exomes 𝑓: 0.62 (280136 hom.)
• Consequence: NPHS2 NM_014625.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.562
• Publications: 44 publications found

Genes affected

NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

AXDND1 (HGNC:26564): (axonemal dynein light chain domain containing 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-179551371-G-A is Benign according to our data. Variant chr1-179551371-G-A is described in ClinVar as Benign. ClinVar VariationId is 260432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.562 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014625.4. 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
	NPHS2	NM_014625.4	MANE Select	c.954C>T	p.Ala318Ala	synonymous	Exon 8 of 8	NP_055440.1	Q9NP85-1
	AXDND1	NM_144696.6	MANE Select	c.3032-3141G>A		intron	N/A	NP_653297.3
	NPHS2	NM_001297575.2		c.750C>T	p.Ala250Ala	synonymous	Exon 7 of 7	NP_001284504.1	Q9NP85-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHS2	ENST00000367615.9	TSL:1 MANE Select	c.954C>T	p.Ala318Ala	synonymous	Exon 8 of 8	ENSP00000356587.4	Q9NP85-1
	NPHS2	ENST00000367616.4	TSL:1	c.750C>T	p.Ala250Ala	synonymous	Exon 7 of 7	ENSP00000356588.4	Q9NP85-2
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.3032-3141G>A		intron	N/A	ENSP00000356590.3	Q5T1B0-1

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93257 AN: 151874 Hom.: 28786 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.608

GnomAD2 exomes AF: 0.619 AC: 155359 AN: 250964 AF XY: 0.618

Gnomad AFR exome AF: 0.600

Gnomad AMR exome AF: 0.665

Gnomad ASJ exome AF: 0.659

Gnomad EAS exome AF: 0.473

Gnomad FIN exome AF: 0.622

Gnomad NFE exome AF: 0.631

Gnomad OTH exome AF: 0.624

GnomAD4 exome AF: 0.618 AC: 903486 AN: 1461802 Hom.: 280136 Cov.: 60 AF XY: 0.618 AC XY: 449545 AN XY: 727192

African (AFR) AF: 0.600 AC: 20089 AN: 33480

American (AMR) AF: 0.663 AC: 29644 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 17217 AN: 26134

East Asian (EAS) AF: 0.507 AC: 20119 AN: 39696

South Asian (SAS) AF: 0.602 AC: 51932 AN: 86254

European-Finnish (FIN) AF: 0.622 AC: 33209 AN: 53418

Middle Eastern (MID) AF: 0.653 AC: 3755 AN: 5750

European-Non Finnish (NFE) AF: 0.621 AC: 690220 AN: 1111962

Other (OTH) AF: 0.618 AC: 37301 AN: 60388

GnomAD4 genome AF: 0.614 AC: 93340 AN: 151994 Hom.: 28814 Cov.: 31 AF XY: 0.613 AC XY: 45530 AN XY: 74282

African (AFR) AF: 0.604 AC: 25029 AN: 41458

American (AMR) AF: 0.639 AC: 9761 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2219 AN: 3466

East Asian (EAS) AF: 0.468 AC: 2411 AN: 5154

South Asian (SAS) AF: 0.591 AC: 2844 AN: 4810

European-Finnish (FIN) AF: 0.619 AC: 6543 AN: 10562

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42480 AN: 67946

Other (OTH) AF: 0.608 AC: 1286 AN: 2114

Alfa AF: 0.626 Hom.: 124683

Bravo AF: 0.616

Asia WGS AF: 0.565 AC: 1966 AN: 3478

EpiCase AF: 0.627

EpiControl AF: 0.628

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	not provided (4)
-	-	2	Nephrotic syndrome, type 2 (2)
-	-	1	Steroid-resistant nephrotic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.17
DANN	Benign	0.63
PhyloP100		-0.56
Mutation Taster		=98/2	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: rs1410592; hg19: chr1-179520506; COSMIC: COSV62634578; COSMIC: COSV62634578;