rs11940192

Positions:

• chr4-72126190-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPFFR2	NM_004885.3	c.-7-2395C>T		intron_variant		ENST00000308744.12
NPFFR2	NM_001144756.2	c.3-2395C>T		intron_variant
NPFFR2	NM_053036.3	c.-7-2395C>T		intron_variant
NPFFR2	XM_011531554.3	c.305-11850C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR2	ENST00000308744.12	c.-7-2395C>T		intron_variant		1	NM_004885.3	P4
NPFFR2	ENST00000344413.6	c.-20-11850C>T		intron_variant		1
NPFFR2	ENST00000358749.3	c.-7-2395C>T		intron_variant		1		P4
NPFFR2	ENST00000395999.5	c.3-2395C>T		intron_variant		1		A2

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

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00756 Hom.: 2

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

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: rs11940192; hg19: chr4-72991907;