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10-70255521-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_022146.5(NPFFR1):c.729C>G(p.Leu243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,548,672 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 1 hom. )

Consequence

NPFFR1
NM_022146.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0260
Variant links:
Genes affected
NPFFR1 (HGNC:17425): (neuropeptide FF receptor 1) Predicted to enable G protein-coupled receptor activity and peptide binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-70255521-G-C is Benign according to our data. Variant chr10-70255521-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 708807.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.026 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000613 (856/1396384) while in subpopulation AFR AF= 0.0164 (517/31506). AF 95% confidence interval is 0.0152. There are 1 homozygotes in gnomad4_exome. There are 361 alleles in male gnomad4_exome subpopulation. Median coverage is 40. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPFFR1NM_022146.5 linkuse as main transcriptc.729C>G p.Leu243= synonymous_variant 4/4 ENST00000277942.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPFFR1ENST00000277942.7 linkuse as main transcriptc.729C>G p.Leu243= synonymous_variant 4/45 NM_022146.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00473
AC:
720
AN:
152170
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0159
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00113
AC:
168
AN:
148862
Hom.:
0
AF XY:
0.000965
AC XY:
77
AN XY:
79784
show subpopulations
Gnomad AFR exome
AF:
0.0150
Gnomad AMR exome
AF:
0.00110
Gnomad ASJ exome
AF:
0.00216
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000441
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000162
Gnomad OTH exome
AF:
0.00117
GnomAD4 exome
AF:
0.000613
AC:
856
AN:
1396384
Hom.:
1
Cov.:
40
AF XY:
0.000524
AC XY:
361
AN XY:
688364
show subpopulations
Gnomad4 AFR exome
AF:
0.0164
Gnomad4 AMR exome
AF:
0.00146
Gnomad4 ASJ exome
AF:
0.00195
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000253
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000129
Gnomad4 OTH exome
AF:
0.00145
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00473
AC:
721
AN:
152288
Hom.:
4
Cov.:
32
AF XY:
0.00439
AC XY:
327
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0158
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00150
Hom.:
0
Bravo
AF:
0.00499
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMar 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
1.3
Dann
Benign
0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140283186; hg19: chr10-72015277; API