chr4-72033374-T-C

Variant names:

• chr4-72033374-T-C
• rs6446796
• NM_004885.3:c.-8+1174T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004885.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPFFR2	NM_004885.3	MANE Select	c.-8+1174T>C		intron	N/A	NP_004876.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPFFR2	ENST00000308744.12	TSL:1 MANE Select	c.-8+1174T>C		intron	N/A	ENSP00000307822.7
	NPFFR2	ENST00000344413.6	TSL:1	c.-21+1174T>C		intron	N/A	ENSP00000340789.6

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

African (AFR) AF: 0.294 AC: 12193 AN: 41472

American (AMR) AF: 0.384 AC: 5876 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3466

East Asian (EAS) AF: 0.668 AC: 3456 AN: 5170

South Asian (SAS) AF: 0.464 AC: 2234 AN: 4816

European-Finnish (FIN) AF: 0.285 AC: 3011 AN: 10576

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.310 AC: 21042 AN: 67948

Other (OTH) AF: 0.366 AC: 774 AN: 2114

Alfa AF: 0.308 Hom.: 932

Bravo AF: 0.339

Asia WGS AF: 0.556 AC: 1929 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6446796; hg19: chr4-72899091;