chr4-72095821-A-C

Variant names:

• chr4-72095821-A-C
• rs12510838
• NM_004885.3:c.-7-32764A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004885.3(NPFFR2):​c.-7-32764A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPFFR2	NM_004885.3	c.-7-32764A>C		intron_variant	Intron 1 of 3	ENST00000308744.12	NP_004876.3
NPFFR2	NM_001144756.2	c.2+26798A>C		intron_variant	Intron 2 of 4		NP_001138228.1
NPFFR2	NM_053036.3	c.-7-32764A>C		intron_variant	Intron 1 of 3		NP_444264.1
NPFFR2	XM_011531554.3	c.305-42219A>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.-7-32764A>C		intron_variant	Intron 1 of 3	1	NM_004885.3	ENSP00000307822.7
NPFFR2	ENST00000395999.5	c.2+26798A>C		intron_variant	Intron 2 of 4	1		ENSP00000379321.1
NPFFR2	ENST00000358749.3	c.-7-32764A>C		intron_variant	Intron 1 of 3	1		ENSP00000351599.3
NPFFR2	ENST00000344413.6	c.-20-42219A>C		intron_variant	Intron 1 of 2	1		ENSP00000340789.6

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.70
PhyloP100		1.5

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: rs12510838; hg19: chr4-72961538;