4-72126190-C-T

Variant names:

• chr4-72126190-C-T
• rs11940192
• NM_004885.3:c.-7-2395C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004885.3(NPFFR2):​c.-7-2395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00951 in 152,230 control chromosomes in the GnomAD database, including 29 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 0.0095 (29 hom., cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.888
• 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=-1.12).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00951 (1448/152230) while in subpopulation AFR AF = 0.0334 (1388/41518). AF 95% confidence interval is 0.032. There are 29 homozygotes in GnomAd4. There are 694 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.-7-2395C>T		intron_variant	Intron 1 of 3	ENST00000308744.12	NP_004876.3
NPFFR2	NM_001144756.2	c.3-2395C>T		intron_variant	Intron 2 of 4		NP_001138228.1
NPFFR2	NM_053036.3	c.-7-2395C>T		intron_variant	Intron 1 of 3		NP_444264.1
NPFFR2	XM_011531554.3	c.305-11850C>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.-7-2395C>T		intron_variant	Intron 1 of 3	1	NM_004885.3	ENSP00000307822.7
NPFFR2	ENST00000395999.5	c.3-2395C>T		intron_variant	Intron 2 of 4	1		ENSP00000379321.1
NPFFR2	ENST00000358749.3	c.-7-2395C>T		intron_variant	Intron 1 of 3	1		ENSP00000351599.3
NPFFR2	ENST00000344413.6	c.-20-11850C>T		intron_variant	Intron 1 of 2	1		ENSP00000340789.6

Frequencies

GnomAD3 genomes AF: 0.00947 AC: 1441 AN: 152112 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00526

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

GnomAD4 genome AF: 0.00951 AC: 1448 AN: 152230 Hom.: 29 Cov.: 32 AF XY: 0.00932 AC XY: 694 AN XY: 74446

African (AFR) AF: 0.0334 AC: 1388 AN: 41518

American (AMR) AF: 0.00248 AC: 38 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68012

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00862 Hom.: 3

Bravo AF: 0.0113

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.74
DANN	Benign	0.75
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism

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: rs11940192; hg19: chr4-72991907;