chr4-72055680-A-G

Variant names:

• chr4-72055680-A-G
• rs10012824
• NM_004885.3:c.-8+23480A>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.-8+23480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 151,734 control chromosomes in the GnomAD database, including 61,356 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 0.89 (61356 hom., cov: 33)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004885.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPFFR2	NM_004885.3	MANE Select	c.-8+23480A>G		intron	N/A	NP_004876.3
	NPFFR2	NM_001144756.2		c.-109-13233A>G		intron	N/A	NP_001138228.1
	NPFFR2	NM_053036.3		c.-8+16267A>G		intron	N/A	NP_444264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPFFR2	ENST00000308744.12	TSL:1 MANE Select	c.-8+23480A>G		intron	N/A	ENSP00000307822.7
	NPFFR2	ENST00000395999.5	TSL:1	c.-109-13233A>G		intron	N/A	ENSP00000379321.1
	NPFFR2	ENST00000358749.3	TSL:1	c.-8+16267A>G		intron	N/A	ENSP00000351599.3

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135129 AN: 151616 Hom.: 61325 Cov.: 33

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.891 AC: 135209 AN: 151734 Hom.: 61356 Cov.: 33 AF XY: 0.890 AC XY: 65993 AN XY: 74146

African (AFR) AF: 0.754 AC: 31169 AN: 41320

American (AMR) AF: 0.901 AC: 13715 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3275 AN: 3462

East Asian (EAS) AF: 0.519 AC: 2660 AN: 5122

South Asian (SAS) AF: 0.873 AC: 4211 AN: 4824

European-Finnish (FIN) AF: 0.980 AC: 10390 AN: 10604

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.983 AC: 66712 AN: 67860

Other (OTH) AF: 0.899 AC: 1896 AN: 2110

Alfa AF: 0.930 Hom.: 3586

Bravo AF: 0.876

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.3
DANN	Benign	0.94
PhyloP100		0.16
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: rs10012824; hg19: chr4-72921397;