10-70260705-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_022146.5(NPFFR1):c.357C>T(p.Ser119=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,608,860 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (3 hom.)
• Consequence: NPFFR1 NM_022146.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 10-70260705-G-A is Benign according to our data. Variant chr10-70260705-G-A is described in ClinVar as [Benign]. Clinvar id is 717656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPFFR1	NM_022146.5	c.357C>T	p.Ser119=	synonymous_variant	3/4	ENST00000277942.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR1	ENST00000277942.7	c.357C>T	p.Ser119=	synonymous_variant	3/4	5	NM_022146.5	P1

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 244 AN: 152146 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00189 AC: 451 AN: 239090 Hom.: 0 AF XY: 0.00195 AC XY: 252 AN XY: 129428

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.000508

Gnomad ASJ exome AF: 0.00788

Gnomad EAS exome AF: 0.000346

Gnomad SAS exome AF: 0.00193

Gnomad FIN exome AF: 0.00220

Gnomad NFE exome AF: 0.00203

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.00188 AC: 2737 AN: 1456596 Hom.: 3 Cov.: 31 AF XY: 0.00194 AC XY: 1408 AN XY: 724006

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.000659

Gnomad4 ASJ exome AF: 0.00718

Gnomad4 EAS exome AF: 0.0000760

Gnomad4 SAS exome AF: 0.00239

Gnomad4 FIN exome AF: 0.00247

Gnomad4 NFE exome AF: 0.00180

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.00160 AC: 244 AN: 152264 Hom.: 2 Cov.: 32 AF XY: 0.00145 AC XY: 108 AN XY: 74446

Gnomad4 AFR AF: 0.000915

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00216 Hom.: 0

Bravo AF: 0.00170

Asia WGS AF: 0.000289 AC: 1 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

Feb 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	8.0
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200754367; hg19: chr10-72020461; COSMIC: COSV53335352;