rs4694453

Positions:

• chr4-72053293-A-C
• chr4-72053293-A-G

Variant summary

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

The NM_004885.3(NPFFR2):​c.-8+21093A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 151,612 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: 30)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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 (NFE) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.-8+21093A>C		intron_variant		ENST00000308744.12	NP_004876.3
NPFFR2	NM_001144756.2	c.-110+13880A>C		intron_variant			NP_001138228.1
NPFFR2	NM_053036.3	c.-8+13880A>C		intron_variant			NP_444264.1
NPFFR2	XM_011531554.3	c.304+13880A>C		intron_variant			XP_011529856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPFFR2	ENST00000308744.12	c.-8+21093A>C		intron_variant		1	NM_004885.3	ENSP00000307822	P4
NPFFR2	ENST00000344413.6	c.-21+21093A>C		intron_variant		1		ENSP00000340789
NPFFR2	ENST00000358749.3	c.-8+13880A>C		intron_variant		1		ENSP00000351599	P4
NPFFR2	ENST00000395999.5	c.-110+13880A>C		intron_variant		1		ENSP00000379321	A2

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135095 AN: 151494 Hom.: 61325 Cov.: 30

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.892 AC: 135175 AN: 151612 Hom.: 61356 Cov.: 30 AF XY: 0.891 AC XY: 65955 AN XY: 74058

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.983

Gnomad4 OTH AF: 0.899

Alfa AF: 0.960 Hom.: 2188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs4694453; hg19: chr4-72919010;