4-72112753-T-C

Variant names:

• chr4-72112753-T-C
• rs4264803
• NM_004885.3:c.-7-15832T>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.-7-15832T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 151,844 control chromosomes in the GnomAD database, including 62,250 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 (62250 hom., cov: 29)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• 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=-1.13).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.-7-15832T>C		intron_variant	Intron 1 of 3	ENST00000308744.12	NP_004876.3
NPFFR2	NM_001144756.2	c.3-15832T>C		intron_variant	Intron 2 of 4		NP_001138228.1
NPFFR2	NM_053036.3	c.-7-15832T>C		intron_variant	Intron 1 of 3		NP_444264.1
NPFFR2	XM_011531554.3	c.305-25287T>C		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.-7-15832T>C		intron_variant	Intron 1 of 3	1	NM_004885.3	ENSP00000307822.7
NPFFR2	ENST00000395999.5	c.3-15832T>C		intron_variant	Intron 2 of 4	1		ENSP00000379321.1
NPFFR2	ENST00000358749.3	c.-7-15832T>C		intron_variant	Intron 1 of 3	1		ENSP00000351599.3
NPFFR2	ENST00000344413.6	c.-20-25287T>C		intron_variant	Intron 1 of 2	1		ENSP00000340789.6

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135272 AN: 151726 Hom.: 62233 Cov.: 29

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.976

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.891 AC: 135334 AN: 151844 Hom.: 62250 Cov.: 29 AF XY: 0.894 AC XY: 66365 AN XY: 74240

African (AFR) AF: 0.636 AC: 26300 AN: 41348

American (AMR) AF: 0.960 AC: 14642 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3455 AN: 3468

East Asian (EAS) AF: 0.994 AC: 5099 AN: 5128

South Asian (SAS) AF: 0.976 AC: 4692 AN: 4808

European-Finnish (FIN) AF: 1.00 AC: 10622 AN: 10624

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67401 AN: 67910

Other (OTH) AF: 0.919 AC: 1934 AN: 2104

Alfa AF: 0.933 Hom.: 8379

Bravo AF: 0.877

Asia WGS AF: 0.955 AC: 3319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.55
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: rs4264803; hg19: chr4-72978470;