1-179551016-C-T

Variant names:

• chr1-179551016-C-T
• rs1410590
• NM_014625.4:c.*157G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014625.4(NPHS2):​c.*157G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 829,342 control chromosomes in the GnomAD database, including 354,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (62802 hom., cov: 32)
  • Exomes 𝑓: 0.93 (291840 hom.)
• Consequence: NPHS2 NM_014625.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.54
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-179551016-C-T is Benign according to our data. Variant chr1-179551016-C-T is described in ClinVar as Benign. ClinVar VariationId is 224483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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.*157G>A		3_prime_UTR	Exon 8 of 8	NP_055440.1	Q9NP85-1
	AXDND1	NM_144696.6	MANE Select	c.3032-3496C>T		intron	N/A	NP_653297.3
	NPHS2	NM_001297575.2		c.*157G>A		3_prime_UTR	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.*157G>A		3_prime_UTR	Exon 8 of 8	ENSP00000356587.4	Q9NP85-1
	NPHS2	ENST00000367616.4	TSL:1	c.*157G>A		3_prime_UTR	Exon 7 of 7	ENSP00000356588.4	Q9NP85-2
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.3032-3496C>T		intron	N/A	ENSP00000356590.3	Q5T1B0-1

Frequencies

GnomAD3 genomes AF: 0.907 AC: 138022 AN: 152136 Hom.: 62758 Cov.: 32

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.928 AC: 628291 AN: 677088 Hom.: 291840 Cov.: 9 AF XY: 0.926 AC XY: 327031 AN XY: 353268

African (AFR) AF: 0.851 AC: 14808 AN: 17400

American (AMR) AF: 0.954 AC: 28642 AN: 30012

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 16426 AN: 18084

East Asian (EAS) AF: 0.971 AC: 31560 AN: 32498

South Asian (SAS) AF: 0.885 AC: 51698 AN: 58440

European-Finnish (FIN) AF: 0.944 AC: 33036 AN: 35014

Middle Eastern (MID) AF: 0.883 AC: 2411 AN: 2732

European-Non Finnish (NFE) AF: 0.932 AC: 418266 AN: 448826

Other (OTH) AF: 0.923 AC: 31444 AN: 34082

GnomAD4 genome AF: 0.907 AC: 138126 AN: 152254 Hom.: 62802 Cov.: 32 AF XY: 0.908 AC XY: 67546 AN XY: 74430

African (AFR) AF: 0.851 AC: 35350 AN: 41518

American (AMR) AF: 0.937 AC: 14326 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3134 AN: 3468

East Asian (EAS) AF: 0.964 AC: 5000 AN: 5186

South Asian (SAS) AF: 0.878 AC: 4234 AN: 4822

European-Finnish (FIN) AF: 0.931 AC: 9885 AN: 10616

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63252 AN: 68032

Other (OTH) AF: 0.894 AC: 1888 AN: 2112

Alfa AF: 0.922 Hom.: 105777

Bravo AF: 0.907

Asia WGS AF: 0.916 AC: 3185 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Nephrotic syndrome, type 2 (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.69
PhyloP100		-1.5
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: rs1410590; hg19: chr1-179520151;