rs551207

Variant names:

• chr1-5947386-C-T
• rs551207
• NM_015102.5:c.993-156G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-5947386-C-T
• chr1-5947386-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015102.5(NPHP4):​c.993-156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,262 control chromosomes in the GnomAD database, including 55,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.85 (55080 hom., cov: 33)
• Consequence: NPHP4 NM_015102.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-5947386-C-T is Benign according to our data. Variant chr1-5947386-C-T is described in ClinVar as Benign. ClinVar VariationId is 1235266.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 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.993-156G>A		intron	N/A	NP_055917.1	O75161-1
	NPHP4	NM_001291594.2		c.-374-156G>A		intron	N/A	NP_001278523.1
	NPHP4	NM_001291593.2		c.-374-156G>A		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.993-156G>A		intron	N/A	ENSP00000367398.4	O75161-1
	NPHP4	ENST00000378169.7	TSL:1	n.*67-156G>A		intron	N/A	ENSP00000367411.3	D6RA06
	NPHP4	ENST00000489180.6	TSL:2	n.993-156G>A		intron	N/A	ENSP00000423747.1	O75161-2

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129295 AN: 152142 Hom.: 55034 Cov.: 33

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.860

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.850 AC: 129400 AN: 152262 Hom.: 55080 Cov.: 33 AF XY: 0.849 AC XY: 63216 AN XY: 74452

African (AFR) AF: 0.845 AC: 35092 AN: 41552

American (AMR) AF: 0.801 AC: 12250 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3043 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3895 AN: 5180

South Asian (SAS) AF: 0.821 AC: 3965 AN: 4830

European-Finnish (FIN) AF: 0.878 AC: 9309 AN: 10600

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.868 AC: 59043 AN: 68008

Other (OTH) AF: 0.862 AC: 1823 AN: 2114

Alfa AF: 0.856 Hom.: 117067

Bravo AF: 0.839

Asia WGS AF: 0.781 AC: 2717 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.22
DANN	Benign	0.41
PhyloP100		-1.1
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: rs551207; hg19: chr1-6007446;