rs6824342

Positions:

• chr4-72037465-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004885.3(NPFFR2):​c.-8+5265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,430 control chromosomes in the GnomAD database, including 9,742 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 0.35 (9742 hom., cov: 30)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.224

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.-8+5265T>C		intron_variant		ENST00000308744.12	NP_004876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPFFR2	ENST00000308744.12	c.-8+5265T>C		intron_variant		1	NM_004885.3	ENSP00000307822	P4
NPFFR2	ENST00000344413.6	c.-21+5265T>C		intron_variant		1		ENSP00000340789

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53089 AN: 151320 Hom.: 9714 Cov.: 30

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.351 AC: 53162 AN: 151430 Hom.: 9742 Cov.: 30 AF XY: 0.352 AC XY: 26044 AN XY: 73976

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.380

Alfa AF: 0.330 Hom.: 1295

Bravo AF: 0.360

Asia WGS AF: 0.561 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.8
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6824342; hg19: chr4-72903182;