rs4129733

Variant names:

• chr4-72097303-T-G
• rs4129733
• NM_004885.3:c.-7-31282T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004885.3(NPFFR2):​c.-7-31282T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,020 control chromosomes in the GnomAD database, including 6,298 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 0.26 (6298 hom., cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.-7-31282T>G		intron_variant	Intron 1 of 3	ENST00000308744.12	NP_004876.3
NPFFR2	NM_001144756.2	c.2+28280T>G		intron_variant	Intron 2 of 4		NP_001138228.1
NPFFR2	NM_053036.3	c.-7-31282T>G		intron_variant	Intron 1 of 3		NP_444264.1
NPFFR2	XM_011531554.3	c.305-40737T>G		intron_variant	Intron 1 of 2		XP_011529856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPFFR2	ENST00000308744.12	c.-7-31282T>G		intron_variant	Intron 1 of 3	1	NM_004885.3	ENSP00000307822.7
NPFFR2	ENST00000395999.5	c.2+28280T>G		intron_variant	Intron 2 of 4	1		ENSP00000379321.1
NPFFR2	ENST00000358749.3	c.-7-31282T>G		intron_variant	Intron 1 of 3	1		ENSP00000351599.3
NPFFR2	ENST00000344413.6	c.-20-40737T>G		intron_variant	Intron 1 of 2	1		ENSP00000340789.6

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39473 AN: 151902 Hom.: 6298 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 39473 AN: 152020 Hom.: 6298 Cov.: 32 AF XY: 0.264 AC XY: 19642 AN XY: 74288

African (AFR) AF: 0.0739 AC: 3070 AN: 41562

American (AMR) AF: 0.347 AC: 5305 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3464

East Asian (EAS) AF: 0.297 AC: 1529 AN: 5156

South Asian (SAS) AF: 0.308 AC: 1488 AN: 4828

European-Finnish (FIN) AF: 0.343 AC: 3608 AN: 10534

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22880 AN: 67896

Other (OTH) AF: 0.242 AC: 510 AN: 2106

Alfa AF: 0.315 Hom.: 4256

Bravo AF: 0.250

Asia WGS AF: 0.275 AC: 952 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.81
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs4129733; hg19: chr4-72963020;