rs6826854

Variant names:

• chr4-72142712-C-T
• rs6826854
• NM_004885.3:c.429-4266C>T

Variant summary

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

The NM_004885.3(NPFFR2):​c.429-4266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 152,214 control chromosomes in the GnomAD database, including 123 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 0.022 (123 hom., cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.429-4266C>T		intron_variant	Intron 3 of 3	ENST00000308744.12	NP_004876.3
NPFFR2	NM_001144756.2	c.438-4266C>T		intron_variant	Intron 4 of 4		NP_001138228.1
NPFFR2	NM_053036.3	c.429-4266C>T		intron_variant	Intron 3 of 3		NP_444264.1
NPFFR2	XM_011531554.3	c.405-4266C>T		intron_variant	Intron 2 of 2		XP_011529856.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPFFR2	ENST00000308744.12	c.429-4266C>T		intron_variant	Intron 3 of 3	1	NM_004885.3	ENSP00000307822.7
NPFFR2	ENST00000395999.5	c.438-4266C>T		intron_variant	Intron 4 of 4	1		ENSP00000379321.1
NPFFR2	ENST00000358749.3	c.429-4266C>T		intron_variant	Intron 3 of 3	1		ENSP00000351599.3
NPFFR2	ENST00000344413.6	c.81-4266C>T		intron_variant	Intron 2 of 2	1		ENSP00000340789.6

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3336 AN: 152096 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0143

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

GnomAD4 genome AF: 0.0220 AC: 3348 AN: 152214 Hom.: 123 Cov.: 32 AF XY: 0.0212 AC XY: 1576 AN XY: 74412

Gnomad4 AFR AF: 0.0764

Gnomad4 AMR AF: 0.00739

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0132 Hom.: 15

Bravo AF: 0.0245

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.42

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: rs6826854; hg19: chr4-73008429;