chr4-72088361-C-T

Variant names:

• chr4-72088361-C-T
• rs9993413
• NM_004885.3:c.-7-40224C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.95).
• 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 rank	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.-7-40224C>T		intron_variant	Intron 1 of 3	ENST00000308744.12	NP_004876.3
NPFFR2	NM_001144756.2	c.2+19338C>T		intron_variant	Intron 2 of 4		NP_001138228.1
NPFFR2	NM_053036.3	c.-7-40224C>T		intron_variant	Intron 1 of 3		NP_444264.1
NPFFR2	XM_011531554.3	c.304+48948C>T		intron_variant	Intron 1 of 2		XP_011529856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPFFR2	ENST00000308744.12	c.-7-40224C>T		intron_variant	Intron 1 of 3	1	NM_004885.3	ENSP00000307822.7
NPFFR2	ENST00000395999.5	c.2+19338C>T		intron_variant	Intron 2 of 4	1		ENSP00000379321.1
NPFFR2	ENST00000358749.3	c.-7-40224C>T		intron_variant	Intron 1 of 3	1		ENSP00000351599.3
NPFFR2	ENST00000344413.6	c.-20-49679C>T		intron_variant	Intron 1 of 2	1		ENSP00000340789.6

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

African (AFR) AF: 0.0625 AC: 2583 AN: 41354

American (AMR) AF: 0.0101 AC: 154 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00395 AC: 19 AN: 4808

European-Finnish (FIN) AF: 0.000190 AC: 2 AN: 10502

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00605 AC: 411 AN: 67880

Other (OTH) AF: 0.0181 AC: 38 AN: 2098

Alfa AF: 0.0128 Hom.: 15

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
PhyloP100		-0.30
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: rs9993413; hg19: chr4-72954078;