rs1079292

Variant names:

• chr1-179575763-T-C
• rs1079292
• NM_014625.4:c.102A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-179575763-T-C
• chr1-179575763-T-A

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.102A>G​(p.Gly34Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,496,666 control chromosomes in the GnomAD database, including 723,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68595 hom., cov: 32)
  • Exomes 𝑓: 0.99 (655374 hom.)
• Consequence: NPHS2 NM_014625.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.412
• Publications: 18 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]

NPHS2 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics, G2P
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 1-179575763-T-C is Benign according to our data. Variant chr1-179575763-T-C is described in ClinVar as Benign. ClinVar VariationId is 260424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.412 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 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.102A>G	p.Gly34Gly	synonymous	Exon 1 of 8	NP_055440.1	Q9NP85-1
	NPHS2	NM_001297575.2		c.102A>G	p.Gly34Gly	synonymous	Exon 1 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.102A>G	p.Gly34Gly	synonymous	Exon 1 of 8	ENSP00000356587.4	Q9NP85-1
	NPHS2	ENST00000367616.4	TSL:1	c.102A>G	p.Gly34Gly	synonymous	Exon 1 of 7	ENSP00000356588.4	Q9NP85-2
	NPHS2	ENST00000902256.1		c.102A>G	p.Gly34Gly	synonymous	Exon 1 of 6	ENSP00000572315.1

Frequencies

GnomAD3 genomes AF: 0.947 AC: 143975 AN: 151962 Hom.: 68551 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.951

GnomAD2 exomes AF: 0.977 AC: 96167 AN: 98386 AF XY: 0.976

Gnomad AFR exome AF: 0.807

Gnomad AMR exome AF: 0.986

Gnomad ASJ exome AF: 0.989

Gnomad EAS exome AF: 0.975

Gnomad FIN exome AF: 0.995

Gnomad NFE exome AF: 0.993

Gnomad OTH exome AF: 0.980

GnomAD4 exome AF: 0.987 AC: 1327035 AN: 1344596 Hom.: 655374 Cov.: 63 AF XY: 0.986 AC XY: 654062 AN XY: 663274

African (AFR) AF: 0.838 AC: 23052 AN: 27496

American (AMR) AF: 0.983 AC: 27848 AN: 28332

Ashkenazi Jewish (ASJ) AF: 0.987 AC: 22789 AN: 23094

East Asian (EAS) AF: 0.977 AC: 31547 AN: 32296

South Asian (SAS) AF: 0.948 AC: 69493 AN: 73330

European-Finnish (FIN) AF: 0.995 AC: 37937 AN: 38122

Middle Eastern (MID) AF: 0.961 AC: 4804 AN: 4998

European-Non Finnish (NFE) AF: 0.994 AC: 1055128 AN: 1061232

Other (OTH) AF: 0.977 AC: 54437 AN: 55696

GnomAD4 genome AF: 0.947 AC: 144070 AN: 152070 Hom.: 68595 Cov.: 32 AF XY: 0.948 AC XY: 70438 AN XY: 74330

African (AFR) AF: 0.844 AC: 35035 AN: 41514

American (AMR) AF: 0.976 AC: 14926 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3431 AN: 3472

East Asian (EAS) AF: 0.978 AC: 4987 AN: 5100

South Asian (SAS) AF: 0.941 AC: 4540 AN: 4826

European-Finnish (FIN) AF: 0.994 AC: 10521 AN: 10588

Middle Eastern (MID) AF: 0.962 AC: 281 AN: 292

European-Non Finnish (NFE) AF: 0.993 AC: 67463 AN: 67954

Other (OTH) AF: 0.951 AC: 2009 AN: 2112

Alfa AF: 0.972 Hom.: 12293

Bravo AF: 0.942

Asia WGS AF: 0.942 AC: 3249 AN: 3450

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Nephrotic syndrome, type 2 (3)
-	-	3	not provided (3)
-	-	1	Steroid-resistant nephrotic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.62
DANN	Benign	0.35
PhyloP100		-0.41
PromoterAI		-0.12	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: rs1079292; hg19: chr1-179544898; COSMIC: COSV62634486; COSMIC: COSV62634486;