rs9993413

Positions:

• chr4-72088361-C-T

Variant summary

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

The NM_004885.3(NPFFR2):​c.-7-40224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 151,664 control chromosomes in the GnomAD database, including 95 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 0.021 (95 hom., cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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 (AFR) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPFFR2	NM_004885.3	c.-7-40224C>T		intron_variant		ENST00000308744.12
NPFFR2	NM_001144756.2	c.2+19338C>T		intron_variant
NPFFR2	NM_053036.3	c.-7-40224C>T		intron_variant
NPFFR2	XM_011531554.3	c.304+48948C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR2	ENST00000308744.12	c.-7-40224C>T		intron_variant		1	NM_004885.3	P4
NPFFR2	ENST00000344413.6	c.-20-49679C>T		intron_variant		1
NPFFR2	ENST00000358749.3	c.-7-40224C>T		intron_variant		1		P4
NPFFR2	ENST00000395999.5	c.2+19338C>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3193 AN: 151546 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00605

Gnomad OTH AF: 0.0183

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

GnomAD4 genome AF: 0.0212 AC: 3214 AN: 151664 Hom.: 95 Cov.: 32 AF XY: 0.0198 AC XY: 1464 AN XY: 74072

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00395

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.00605

Gnomad4 OTH AF: 0.0181

Alfa AF: 0.0117 Hom.: 6

Bravo AF: 0.0236

Asia WGS AF: 0.00665 AC: 23 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.39
DANN	Benign	0.17

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: rs9993413; hg19: chr4-72954078;