chr1-179550745-T-C

Variant names:

• chr1-179550745-T-C
• rs1060775
• NM_014625.4:c.*428A>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.*428A>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 0.912 in 220,034 control chromosomes in the GnomAD database, including 91,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (62401 hom., cov: 30)
  • Exomes 𝑓: 0.93 (29333 hom.)
• Consequence: NPHS2 NM_014625.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.264
• Publications: 2 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=-0.89).
• BP6: Variant 1-179550745-T-C is Benign according to our data. Variant chr1-179550745-T-C is described in ClinVar as Benign. ClinVar VariationId is 224486.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.*428A>G		3_prime_UTR	Exon 8 of 8	NP_055440.1	Q9NP85-1
	AXDND1	NM_144696.6	MANE Select	c.3032-3767T>C		intron	N/A	NP_653297.3
	NPHS2	NM_001297575.2		c.*428A>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.*428A>G		3_prime_UTR	Exon 8 of 8	ENSP00000356587.4	Q9NP85-1
	NPHS2	ENST00000367616.4	TSL:1	c.*428A>G		3_prime_UTR	Exon 7 of 7	ENSP00000356588.4	Q9NP85-2
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.3032-3767T>C		intron	N/A	ENSP00000356590.3	Q5T1B0-1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137506 AN: 152026 Hom.: 62357 Cov.: 30

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.936

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: 0.891

GnomAD4 exome AF: 0.929 AC: 63050 AN: 67890 Hom.: 29333 Cov.: 0 AF XY: 0.925 AC XY: 32032 AN XY: 34612

African (AFR) AF: 0.839 AC: 2103 AN: 2508

American (AMR) AF: 0.949 AC: 3953 AN: 4166

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 1513 AN: 1650

East Asian (EAS) AF: 0.964 AC: 4130 AN: 4284

South Asian (SAS) AF: 0.884 AC: 6643 AN: 7512

European-Finnish (FIN) AF: 0.946 AC: 2453 AN: 2594

Middle Eastern (MID) AF: 0.848 AC: 229 AN: 270

European-Non Finnish (NFE) AF: 0.937 AC: 38539 AN: 41130

Other (OTH) AF: 0.923 AC: 3487 AN: 3776

GnomAD4 genome AF: 0.904 AC: 137608 AN: 152144 Hom.: 62401 Cov.: 30 AF XY: 0.905 AC XY: 67303 AN XY: 74374

African (AFR) AF: 0.842 AC: 34913 AN: 41478

American (AMR) AF: 0.936 AC: 14307 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3136 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4980 AN: 5164

South Asian (SAS) AF: 0.878 AC: 4223 AN: 4810

European-Finnish (FIN) AF: 0.931 AC: 9873 AN: 10602

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

European-Non Finnish (NFE) AF: 0.930 AC: 63236 AN: 68018

Other (OTH) AF: 0.892 AC: 1883 AN: 2110

Alfa AF: 0.920 Hom.: 54308

Bravo AF: 0.904

Asia WGS AF: 0.915 AC: 3182 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Nephrotic syndrome, type 2 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.41
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: rs1060775; hg19: chr1-179519880;