chr4-72033374-T-C

Position:

• chr4-72033374-T-C

Variant summary

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

The NM_004885.3(NPFFR2):​c.-8+1174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,046 control chromosomes in the GnomAD database, including 8,834 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 0.33 (8834 hom., cov: 32)
• Consequence: NPFFR2 NM_004885.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924

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 (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPFFR2	NM_004885.3	c.-8+1174T>C		intron_variant		ENST00000308744.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPFFR2	ENST00000308744.12	c.-8+1174T>C		intron_variant		1	NM_004885.3	P4
NPFFR2	ENST00000344413.6	c.-21+1174T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50446 AN: 151924 Hom.: 8821 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.413

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.332 AC: 50493 AN: 152046 Hom.: 8834 Cov.: 32 AF XY: 0.334 AC XY: 24834 AN XY: 74328

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.366

Alfa AF: 0.308 Hom.: 899

Bravo AF: 0.339

Asia WGS AF: 0.556 AC: 1929 AN: 3470

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	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6446796; hg19: chr4-72899091;