rs6446809

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004885.3(NPFFR2):​c.-8+27577T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 152,188 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 32)

Consequence

NPFFR2
NM_004885.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0410
Variant links:
Genes affected
NPFFR2 (HGNC:4525): (neuropeptide FF receptor 2) This gene encodes a member of a subfamily of G-protein-coupled neuropeptide receptors. This protein is activated by the neuropeptides A-18-amide (NPAF) and F-8-amide (NPFF) and may function in pain modulation and regulation of the opioid system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BS2
High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NPFFR2NM_004885.3 linkuse as main transcriptc.-8+27577T>G intron_variant ENST00000308744.12 NP_004876.3 Q9Y5X5-2A0PJM9
NPFFR2NM_001144756.2 linkuse as main transcriptc.-109-9136T>G intron_variant NP_001138228.1 Q9Y5X5-3A0PJM9
NPFFR2NM_053036.3 linkuse as main transcriptc.-8+20364T>G intron_variant NP_444264.1 Q9Y5X5-2A0PJM9
NPFFR2XM_011531554.3 linkuse as main transcriptc.304+20364T>G intron_variant XP_011529856.2 A0A804CC06

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NPFFR2ENST00000308744.12 linkuse as main transcriptc.-8+27577T>G intron_variant 1 NM_004885.3 ENSP00000307822.7 Q9Y5X5-2
NPFFR2ENST00000395999.5 linkuse as main transcriptc.-109-9136T>G intron_variant 1 ENSP00000379321.1 Q9Y5X5-3
NPFFR2ENST00000358749.3 linkuse as main transcriptc.-8+20364T>G intron_variant 1 ENSP00000351599.3 Q9Y5X5-2
NPFFR2ENST00000344413.6 linkuse as main transcriptc.-21+27577T>G intron_variant 1 ENSP00000340789.6 A0A804CC06

Frequencies

GnomAD3 genomes
AF:
0.00586
AC:
891
AN:
152070
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00970
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0108
Gnomad ASJ
AF:
0.0548
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.00144
Gnomad OTH
AF:
0.0106
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00588
AC:
895
AN:
152188
Hom.:
8
Cov.:
32
AF XY:
0.00567
AC XY:
422
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.00977
Gnomad4 AMR
AF:
0.0108
Gnomad4 ASJ
AF:
0.0548
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.00144
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00469
Hom.:
1
Bravo
AF:
0.00711
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
2.2
DANN
Benign
0.39

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: rs6446809; hg19: chr4-72925494; API