rs114900019

Variant names:

• chr1-5907106-G-A
• rs114900019
• NM_015102.5:c.1611+9C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-5907106-G-A
• chr1-5907106-G-T

Variant summary

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

The NM_015102.5(NPHP4):​c.1611+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,472,948 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (59 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (48 hom.)
• Consequence: NPHP4 NM_015102.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.83
• Publications: 0 publications found

Genes affected

NPHP4 (HGNC:19104): (nephrocystin 4) This gene encodes a protein involved in renal tubular development and function. This protein interacts with nephrocystin, and belongs to a multifunctional complex that is localized to actin- and microtubule-based structures. Mutations in this gene are associated with nephronophthisis type 4, a renal disease, and with Senior-Loken syndrome type 4, a combination of nephronophthisis and retinitis pigmentosa. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

NPHP4 Gene-Disease associations (from GenCC):

• nephronophthisis 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Senior-Loken syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• nephronophthisis 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-5907106-G-A is Benign according to our data. Variant chr1-5907106-G-A is described in ClinVar as Benign. ClinVar VariationId is 95672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015102.5. 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
	NPHP4	NM_015102.5	MANE Select	c.1611+9C>T		intron	N/A	NP_055917.1	O75161-1
	NPHP4	NM_001291594.2		c.76-1323C>T		intron	N/A	NP_001278523.1
	NPHP4	NM_001291593.2		c.76-1326C>T		intron	N/A	NP_001278522.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP4	ENST00000378156.9	TSL:1 MANE Select	c.1611+9C>T		intron	N/A	ENSP00000367398.4	O75161-1
	NPHP4	ENST00000378169.7	TSL:1	n.*516-1326C>T		intron	N/A	ENSP00000367411.3	D6RA06
	NPHP4	ENST00000489180.6	TSL:2	n.1611+9C>T		intron	N/A	ENSP00000423747.1	O75161-2

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2304 AN: 152238 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00395 AC: 523 AN: 132392 AF XY: 0.00321

Gnomad AFR exome AF: 0.0544

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000135

Gnomad NFE exome AF: 0.000245

Gnomad OTH exome AF: 0.00176

GnomAD4 exome AF: 0.00161 AC: 2128 AN: 1320592 Hom.: 48 Cov.: 21 AF XY: 0.00146 AC XY: 950 AN XY: 648768

African (AFR) AF: 0.0551 AC: 1622 AN: 29440

American (AMR) AF: 0.00409 AC: 124 AN: 30330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22146

East Asian (EAS) AF: 0.00 AC: 0 AN: 34136

South Asian (SAS) AF: 0.000117 AC: 8 AN: 68616

European-Finnish (FIN) AF: 0.0000410 AC: 2 AN: 48770

Middle Eastern (MID) AF: 0.00341 AC: 18 AN: 5286

European-Non Finnish (NFE) AF: 0.000140 AC: 144 AN: 1027138

Other (OTH) AF: 0.00384 AC: 210 AN: 54730

GnomAD4 genome AF: 0.0152 AC: 2317 AN: 152356 Hom.: 59 Cov.: 33 AF XY: 0.0147 AC XY: 1095 AN XY: 74514

African (AFR) AF: 0.0531 AC: 2209 AN: 41584

American (AMR) AF: 0.00431 AC: 66 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68022

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.00901 Hom.: 19

Bravo AF: 0.0166

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Kidney disorder (1)
-	-	1	Nephronophthisis (1)
-	-	1	Nephronophthisis 4 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Senior-Loken syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs114900019; hg19: chr1-5967166;