rs13107347

chr4-72109031-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.-7-19554T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,868 control chromosomes in the GnomAD database, including 8,104 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 0.32 (8104 hom., cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPFFR2	NM_004885.3	c.-7-19554T>C		intron_variant		ENST00000308744.12
NPFFR2	NM_001144756.2	c.3-19554T>C		intron_variant
NPFFR2	NM_053036.3	c.-7-19554T>C		intron_variant
NPFFR2	XM_011531554.3	c.305-29009T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR2	ENST00000308744.12	c.-7-19554T>C		intron_variant		1	NM_004885.3	P4
NPFFR2	ENST00000344413.6	c.-20-29009T>C		intron_variant		1
NPFFR2	ENST00000358749.3	c.-7-19554T>C		intron_variant		1		P4
NPFFR2	ENST00000395999.5	c.3-19554T>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48333 AN: 151748 Hom.: 8100 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.318 AC: 48353 AN: 151868 Hom.: 8104 Cov.: 32 AF XY: 0.319 AC XY: 23706 AN XY: 74214

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.347

Alfa AF: 0.344 Hom.: 5753

Bravo AF: 0.314

Asia WGS AF: 0.400 AC: 1388 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.1
Dann	Benign	0.50

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: rs13107347; hg19: chr4-72974748;