1-179550915-T-C

Variant names:

• chr1-179550915-T-C
• rs2274622
• NM_014625.4:c.*258A>G

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.*258A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 512,930 control chromosomes in the GnomAD database, including 20,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4898 hom., cov: 32)
  • Exomes 𝑓: 0.29 (15691 hom.)
• Consequence: NPHS2 NM_014625.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.259
• Publications: 15 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=-0.82).
• BP6: Variant 1-179550915-T-C is Benign according to our data. Variant chr1-179550915-T-C is described in ClinVar as Benign. ClinVar VariationId is 224485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 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.*258A>G		3_prime_UTR	Exon 8 of 8	NP_055440.1	Q9NP85-1
	AXDND1	NM_144696.6	MANE Select	c.3032-3597T>C		intron	N/A	NP_653297.3
	NPHS2	NM_001297575.2		c.*258A>G		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.*258A>G		3_prime_UTR	Exon 8 of 8	ENSP00000356587.4	Q9NP85-1
	NPHS2	ENST00000367616.4	TSL:1	c.*258A>G		3_prime_UTR	Exon 7 of 7	ENSP00000356588.4	Q9NP85-2
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.3032-3597T>C		intron	N/A	ENSP00000356590.3	Q5T1B0-1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36751 AN: 151984 Hom.: 4892 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.286 AC: 103298 AN: 360826 Hom.: 15691 Cov.: 4 AF XY: 0.290 AC XY: 55549 AN XY: 191260

African (AFR) AF: 0.130 AC: 1377 AN: 10584

American (AMR) AF: 0.295 AC: 4674 AN: 15830

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 2718 AN: 10982

East Asian (EAS) AF: 0.383 AC: 8613 AN: 22502

South Asian (SAS) AF: 0.341 AC: 14657 AN: 42920

European-Finnish (FIN) AF: 0.229 AC: 4520 AN: 19698

Middle Eastern (MID) AF: 0.322 AC: 496 AN: 1542

European-Non Finnish (NFE) AF: 0.280 AC: 60447 AN: 216230

Other (OTH) AF: 0.282 AC: 5796 AN: 20538

GnomAD4 genome AF: 0.242 AC: 36768 AN: 152104 Hom.: 4898 Cov.: 32 AF XY: 0.243 AC XY: 18041 AN XY: 74352

African (AFR) AF: 0.127 AC: 5274 AN: 41518

American (AMR) AF: 0.302 AC: 4617 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 823 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1840 AN: 5160

South Asian (SAS) AF: 0.351 AC: 1690 AN: 4818

European-Finnish (FIN) AF: 0.231 AC: 2451 AN: 10592

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19103 AN: 67966

Other (OTH) AF: 0.271 AC: 572 AN: 2110

Alfa AF: 0.273 Hom.: 18749

Bravo AF: 0.241

Asia WGS AF: 0.374 AC: 1301 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.82
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		0.26
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: rs2274622; hg19: chr1-179520050;