chr2-110163152-C-T

Variant names:

• chr2-110163152-C-T
• rs146343637
• NM_001128178.3:c.772-17G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001128178.3(NPHP1):​c.772-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00858 in 1,558,244 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (130 hom.)
• Consequence: NPHP1 NM_001128178.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.851
• Publications: 0 publications found

Genes affected

NPHP1 (HGNC:7905): (nephrocystin 1) This gene encodes a protein with src homology domain 3 (SH3) patterns. This protein interacts with Crk-associated substrate, and it appears to function in the control of cell division, as well as in cell-cell and cell-matrix adhesion signaling, likely as part of a multifunctional complex localized in actin- and microtubule-based structures. Mutations in this gene cause familial juvenile nephronophthisis type 1, a kidney disorder involving both tubules and glomeruli. Defects in this gene are also associated with Senior-Loken syndrome type 1, also referred to as juvenile nephronophthisis with Leber amaurosis, which is characterized by kidney and eye disease, and with Joubert syndrome type 4, which is characterized by cerebellar ataxia, oculomotor apraxia, psychomotor delay and neonatal breathing abnormalities, sometimes including retinal dystrophy and renal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

NPHP1 Gene-Disease associations (from GenCC):

• Joubert syndrome with renal defect

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P
• nephronophthisis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• Bardet-Biedl syndrome

  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=-0.86).
• BP6: Variant 2-110163152-C-T is Benign according to our data. Variant chr2-110163152-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 199003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00835 (1272/152250) while in subpopulation NFE AF = 0.00878 (597/68008). AF 95% confidence interval is 0.0082. There are 15 homozygotes in GnomAd4. There are 674 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128178.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP1	NM_001128178.3	MANE Select	c.772-17G>A		intron	N/A	NP_001121650.1
	NPHP1	NM_000272.5		c.940-17G>A		intron	N/A	NP_000263.2
	NPHP1	NM_207181.4		c.940-20G>A		intron	N/A	NP_997064.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP1	ENST00000445609.7	TSL:1 MANE Select	c.772-17G>A		intron	N/A	ENSP00000389879.3
	NPHP1	ENST00000316534.8	TSL:1	c.940-17G>A		intron	N/A	ENSP00000313169.4
	NPHP1	ENST00000393272.7	TSL:1	c.940-20G>A		intron	N/A	ENSP00000376953.3

Frequencies

GnomAD3 genomes AF: 0.00836 AC: 1272 AN: 152132 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.0400

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00878

Gnomad OTH AF: 0.00957

GnomAD2 exomes AF: 0.0102 AC: 2567 AN: 250642 AF XY: 0.0105

Gnomad AFR exome AF: 0.000987

Gnomad AMR exome AF: 0.00429

Gnomad ASJ exome AF: 0.0287

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0444

Gnomad NFE exome AF: 0.00830

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.00861 AC: 12105 AN: 1405994 Hom.: 130 Cov.: 24 AF XY: 0.00869 AC XY: 6108 AN XY: 702942

African (AFR) AF: 0.000862 AC: 28 AN: 32490

American (AMR) AF: 0.00414 AC: 185 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 773 AN: 25796

East Asian (EAS) AF: 0.00 AC: 0 AN: 39400

South Asian (SAS) AF: 0.00551 AC: 469 AN: 85128

European-Finnish (FIN) AF: 0.0435 AC: 2323 AN: 53350

Middle Eastern (MID) AF: 0.0140 AC: 79 AN: 5648

European-Non Finnish (NFE) AF: 0.00726 AC: 7705 AN: 1060936

Other (OTH) AF: 0.00927 AC: 543 AN: 58596

GnomAD4 genome AF: 0.00835 AC: 1272 AN: 152250 Hom.: 15 Cov.: 32 AF XY: 0.00905 AC XY: 674 AN XY: 74444

African (AFR) AF: 0.000938 AC: 39 AN: 41564

American (AMR) AF: 0.00386 AC: 59 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3466

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4816

European-Finnish (FIN) AF: 0.0400 AC: 424 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00878 AC: 597 AN: 68008

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.0127 Hom.: 4

Bravo AF: 0.00504

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Sep 18, 2014

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Oct 16, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NPHP1: BS2

Nephronophthisis Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.30
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs146343637; hg19: chr2-110920729; COSMIC: COSV57209105;