NM_004885.3:c.-8+21093A>C

Variant names:

• chr4-72053293-A-C
• rs4694453
• NM_004885.3:c.-8+21093A>C

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+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
• 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=-0.98).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPFFR2	NM_004885.3	MANE Select	c.-8+21093A>C		intron	N/A	NP_004876.3	Q9Y5X5-2
	NPFFR2	NM_001144756.2		c.-110+13880A>C		intron	N/A	NP_001138228.1	Q9Y5X5-3
	NPFFR2	NM_053036.3		c.-8+13880A>C		intron	N/A	NP_444264.1	Q9Y5X5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPFFR2	ENST00000308744.12	TSL:1 MANE Select	c.-8+21093A>C		intron	N/A	ENSP00000307822.7	Q9Y5X5-2
	NPFFR2	ENST00000395999.5	TSL:1	c.-110+13880A>C		intron	N/A	ENSP00000379321.1	Q9Y5X5-3
	NPFFR2	ENST00000358749.3	TSL:1	c.-8+13880A>C		intron	N/A	ENSP00000351599.3	Q9Y5X5-2

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

African (AFR) AF: 0.755 AC: 31214 AN: 41316

American (AMR) AF: 0.900 AC: 13673 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3276 AN: 3464

East Asian (EAS) AF: 0.524 AC: 2680 AN: 5110

South Asian (SAS) AF: 0.873 AC: 4191 AN: 4802

European-Finnish (FIN) AF: 0.980 AC: 10357 AN: 10570

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

European-Non Finnish (NFE) AF: 0.983 AC: 66707 AN: 67854

Other (OTH) AF: 0.899 AC: 1894 AN: 2106

Alfa AF: 0.960 Hom.: 2188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.13
PhyloP100		-0.17
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: rs4694453; hg19: chr4-72919010;