4-72132192-C-T

Variant names:

• chr4-72132192-C-T
• rs7679840
• NM_004885.3:c.328+3273C>T

Variant summary

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

The NM_004885.3(NPFFR2):​c.328+3273C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 151,542 control chromosomes in the GnomAD database, including 532 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 0.045 (532 hom., cov: 31)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 0 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.328+3273C>T		intron_variant	Intron 2 of 3	ENST00000308744.12	NP_004876.3
NPFFR2	NM_001144756.2	c.337+3273C>T		intron_variant	Intron 3 of 4		NP_001138228.1
NPFFR2	NM_053036.3	c.328+3273C>T		intron_variant	Intron 2 of 3		NP_444264.1
NPFFR2	XM_011531554.3	c.305-5848C>T		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.328+3273C>T		intron_variant	Intron 2 of 3	1	NM_004885.3	ENSP00000307822.7
NPFFR2	ENST00000395999.5	c.337+3273C>T		intron_variant	Intron 3 of 4	1		ENSP00000379321.1
NPFFR2	ENST00000358749.3	c.328+3273C>T		intron_variant	Intron 2 of 3	1		ENSP00000351599.3
NPFFR2	ENST00000344413.6	c.-20-5848C>T		intron_variant	Intron 1 of 2	1		ENSP00000340789.6

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6798 AN: 151426 Hom.: 532 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0369

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

GnomAD4 genome AF: 0.0449 AC: 6806 AN: 151542 Hom.: 532 Cov.: 31 AF XY: 0.0433 AC XY: 3205 AN XY: 74074

African (AFR) AF: 0.155 AC: 6368 AN: 41188

American (AMR) AF: 0.0175 AC: 266 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00318 AC: 11 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5152

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4810

European-Finnish (FIN) AF: 0.000191 AC: 2 AN: 10498

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 67896

Other (OTH) AF: 0.0366 AC: 77 AN: 2106

Alfa AF: 0.0119 Hom.: 18

Bravo AF: 0.0518

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.59
DANN	Benign	0.22
PhyloP100		-1.9
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: rs7679840; hg19: chr4-72997909;