rs1018541634

Variant names:

• chr10-70255034-C-A
• rs1018541634
• NM_022146.5:c.1216G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-70255034-C-A
• chr10-70255034-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022146.5(NPFFR1):​c.1216G>T​(p.Val406Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000776 in 1,288,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V406M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: NPFFR1 NM_022146.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18389761).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022146.5. 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
	NPFFR1	NM_022146.5	MANE Select	c.1216G>T	p.Val406Leu	missense	Exon 4 of 4	NP_071429.1	Q9GZQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPFFR1	ENST00000277942.7	TSL:5 MANE Select	c.1216G>T	p.Val406Leu	missense	Exon 4 of 4	ENSP00000277942.5	Q9GZQ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000776 AC: 10 AN: 1288494 Hom.: 0 Cov.: 40 AF XY: 0.00000797 AC XY: 5 AN XY: 627588

African (AFR) AF: 0.00 AC: 0 AN: 25544

American (AMR) AF: 0.00 AC: 0 AN: 18874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18188

East Asian (EAS) AF: 0.000275 AC: 9 AN: 32774

South Asian (SAS) AF: 0.00 AC: 0 AN: 62190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4904

European-Non Finnish (NFE) AF: 9.65e-7 AC: 1 AN: 1036206

Other (OTH) AF: 0.00 AC: 0 AN: 53402

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.087
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.049	D
Polyphen		0.48	P
Vest4		0.096
MutPred		0.31		Loss of MoRF binding (P = 0.0946)
MVP		0.82
MPC		1.1
ClinPred		0.53	D
GERP RS		4.0
Varity_R		0.10
gMVP		0.45
Mutation Taster		=97/3	polymorphism

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: rs1018541634; hg19: chr10-72014790;