NM_004885.3:c.-8+34978T>A

Variant names:

• chr4-72067178-T-A
• rs4353870
• NM_004885.3:c.-8+34978T>A

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+34978T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,092 control chromosomes in the GnomAD database, including 62,426 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 0.90 (62426 hom., cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.976 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+34978T>A		intron	N/A	NP_004876.3
	NPFFR2	NM_001144756.2		c.-109-1735T>A		intron	N/A	NP_001138228.1
	NPFFR2	NM_053036.3		c.-8+27765T>A		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+34978T>A		intron	N/A	ENSP00000307822.7
	NPFFR2	ENST00000395999.5	TSL:1	c.-109-1735T>A		intron	N/A	ENSP00000379321.1
	NPFFR2	ENST00000358749.3	TSL:1	c.-8+27765T>A		intron	N/A	ENSP00000351599.3

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136658 AN: 151976 Hom.: 62394 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.899 AC: 136739 AN: 152092 Hom.: 62426 Cov.: 32 AF XY: 0.898 AC XY: 66743 AN XY: 74354

African (AFR) AF: 0.784 AC: 32546 AN: 41526

American (AMR) AF: 0.904 AC: 13819 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3259 AN: 3456

East Asian (EAS) AF: 0.527 AC: 2704 AN: 5132

South Asian (SAS) AF: 0.874 AC: 4214 AN: 4824

European-Finnish (FIN) AF: 0.979 AC: 10386 AN: 10612

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

European-Non Finnish (NFE) AF: 0.982 AC: 66725 AN: 67932

Other (OTH) AF: 0.902 AC: 1903 AN: 2110

Alfa AF: 0.940 Hom.: 8356

Bravo AF: 0.885

Asia WGS AF: 0.710 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.48
PhyloP100		0.20
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: rs4353870; hg19: chr4-72932895;