chr1-179551119-C-G

Variant names:

• chr1-179551119-C-G
• rs1410591
• NM_014625.4:c.*54G>C

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.*54G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,607,334 control chromosomes in the GnomAD database, including 309,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28879 hom., cov: 31)
  • Exomes 𝑓: 0.62 (280283 hom.)
• Consequence: NPHS2 NM_014625.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.952
• Publications: 11 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=-0.9).
• BP6: Variant 1-179551119-C-G is Benign according to our data. Variant chr1-179551119-C-G is described in ClinVar as Benign. ClinVar VariationId is 293845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.*54G>C		3_prime_UTR	Exon 8 of 8	NP_055440.1	Q9NP85-1
	AXDND1	NM_144696.6	MANE Select	c.3032-3393C>G		intron	N/A	NP_653297.3
	NPHS2	NM_001297575.2		c.*54G>C		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.*54G>C		3_prime_UTR	Exon 8 of 8	ENSP00000356587.4	Q9NP85-1
	NPHS2	ENST00000367616.4	TSL:1	c.*54G>C		3_prime_UTR	Exon 7 of 7	ENSP00000356588.4	Q9NP85-2
	AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.3032-3393C>G		intron	N/A	ENSP00000356590.3	Q5T1B0-1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93387 AN: 151920 Hom.: 28851 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.608

GnomAD4 exome AF: 0.620 AC: 901687 AN: 1455296 Hom.: 280283 Cov.: 30 AF XY: 0.620 AC XY: 448858 AN XY: 724316

African (AFR) AF: 0.601 AC: 20049 AN: 33370

American (AMR) AF: 0.664 AC: 29640 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 17193 AN: 26094

East Asian (EAS) AF: 0.507 AC: 20098 AN: 39648

South Asian (SAS) AF: 0.602 AC: 51736 AN: 85910

European-Finnish (FIN) AF: 0.624 AC: 32612 AN: 52254

Middle Eastern (MID) AF: 0.654 AC: 3754 AN: 5740

European-Non Finnish (NFE) AF: 0.622 AC: 689339 AN: 1107446

Other (OTH) AF: 0.619 AC: 37266 AN: 60188

GnomAD4 genome AF: 0.615 AC: 93471 AN: 152038 Hom.: 28879 Cov.: 31 AF XY: 0.613 AC XY: 45580 AN XY: 74302

African (AFR) AF: 0.604 AC: 25028 AN: 41452

American (AMR) AF: 0.639 AC: 9763 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2221 AN: 3470

East Asian (EAS) AF: 0.468 AC: 2418 AN: 5162

South Asian (SAS) AF: 0.591 AC: 2846 AN: 4814

European-Finnish (FIN) AF: 0.620 AC: 6560 AN: 10574

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

European-Non Finnish (NFE) AF: 0.626 AC: 42582 AN: 67970

Other (OTH) AF: 0.609 AC: 1284 AN: 2110

Alfa AF: 0.509 Hom.: 1425

Bravo AF: 0.617

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.44
PhyloP100		0.95
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: rs1410591; hg19: chr1-179520254; COSMIC: COSV62634863; COSMIC: COSV62634863;