rs9291171

Variant names:

• chr4-72115909-A-G
• rs9291171
• NM_004885.3:c.-7-12676A>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.-7-12676A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,104 control chromosomes in the GnomAD database, including 5,839 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 0.27 (5839 hom., cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 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.-7-12676A>G		intron	N/A	NP_004876.3
	NPFFR2	NM_001144756.2		c.3-12676A>G		intron	N/A	NP_001138228.1
	NPFFR2	NM_053036.3		c.-7-12676A>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.-7-12676A>G		intron	N/A	ENSP00000307822.7
	NPFFR2	ENST00000395999.5	TSL:1	c.3-12676A>G		intron	N/A	ENSP00000379321.1
	NPFFR2	ENST00000358749.3	TSL:1	c.-7-12676A>G		intron	N/A	ENSP00000351599.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40838 AN: 151986 Hom.: 5828 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.269 AC: 40866 AN: 152104 Hom.: 5839 Cov.: 32 AF XY: 0.267 AC XY: 19884 AN XY: 74350

African (AFR) AF: 0.180 AC: 7484 AN: 41512

American (AMR) AF: 0.301 AC: 4595 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1042 AN: 5168

South Asian (SAS) AF: 0.335 AC: 1616 AN: 4826

European-Finnish (FIN) AF: 0.265 AC: 2807 AN: 10576

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20924 AN: 67970

Other (OTH) AF: 0.298 AC: 630 AN: 2112

Alfa AF: 0.266 Hom.: 994

Bravo AF: 0.265

Asia WGS AF: 0.272 AC: 945 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.8
DANN	Benign	0.73
PhyloP100		-0.065
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: rs9291171; hg19: chr4-72981626;