10-70255673-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_022146.5(NPFFR1):c.577G>T(p.Ala193Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,602,180 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (32 hom.)
• Consequence: NPFFR1 NM_022146.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.144

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002101928).
• BP6: Variant 10-70255673-C-A is Benign according to our data. Variant chr10-70255673-C-A is described in ClinVar as [Benign]. Clinvar id is 776517.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1602/152292) while in subpopulation AFR AF= 0.0359 (1493/41578). AF 95% confidence interval is 0.0344. There are 26 homozygotes in gnomad4. There are 751 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPFFR1	NM_022146.5	c.577G>T	p.Ala193Ser	missense_variant	4/4	ENST00000277942.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR1	ENST00000277942.7	c.577G>T	p.Ala193Ser	missense_variant	4/4	5	NM_022146.5	P1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1595 AN: 152174 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00726

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00338 AC: 756 AN: 223904 Hom.: 13 AF XY: 0.00283 AC XY: 345 AN XY: 122036

Gnomad AFR exome AF: 0.0363

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.000104

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00638

Gnomad FIN exome AF: 0.0000535

Gnomad NFE exome AF: 0.000301

Gnomad OTH exome AF: 0.00144

GnomAD4 exome AF: 0.00153 AC: 2216 AN: 1449888 Hom.: 32 Cov.: 37 AF XY: 0.00157 AC XY: 1132 AN XY: 720032

Gnomad4 AFR exome AF: 0.0363

Gnomad4 AMR exome AF: 0.00207

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00626

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.000192

Gnomad4 OTH exome AF: 0.00267

GnomAD4 genome AF: 0.0105 AC: 1602 AN: 152292 Hom.: 26 Cov.: 32 AF XY: 0.0101 AC XY: 751 AN XY: 74460

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00706

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00205 Hom.: 4

Bravo AF: 0.0117

ESP6500AA AF: 0.0367 AC: 161

ESP6500EA AF: 0.000467 AC: 4

ExAC AF: 0.00389 AC: 471

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	16
Dann	Benign	0.91
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.0048
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	0.82	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.13
Sift	Benign	0.88	T
Sift4G	Benign	0.85	T
Polyphen		0.77	P
Vest4		0.065
MVP		0.60
MPC		1.5
ClinPred		0.041	T
GERP RS		4.3
Varity_R		0.071
gMVP		0.46

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

Other links and lift over

dbSNP: rs61746115; hg19: chr10-72015429;