4-155206897-A-G

Variant names:

• chr4-155206897-A-G
• rs4333136
• NM_001375470.1:c.-48-6995A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375470.1(NPY2R):​c.-48-6995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,986 control chromosomes in the GnomAD database, including 20,135 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 0.49 (20135 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: NPY2R NM_001375470.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 3 publications found

Genes affected

NPY2R (HGNC:7957): (neuropeptide Y receptor Y2) Predicted to enable calcium channel regulator activity and neuropeptide Y receptor activity. Involved in cardiac left ventricle morphogenesis and outflow tract morphogenesis. Located in cilium. Implicated in Huntington's disease; morbid obesity; and obesity. Biomarker of peripheral artery disease and temporal lobe epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

NPY2R-AS1 (HGNC:55549): (NPY2R antisense RNA 1)

MAP9-AS1 (HGNC:56110): (MAP9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375470.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R	NM_001375470.1		c.-48-6995A>G		intron	N/A	NP_001362399.1	P49146

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY2R-AS1	ENST00000511017.7	TSL:3	n.1323T>C		non_coding_transcript_exon	Exon 3 of 3
	MAP9-AS1	ENST00000630664.3	TSL:5	n.399+32613A>G		intron	N/A
	NPY2R-AS1	ENST00000727157.1		n.361+1128T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75062 AN: 151864 Hom.: 20089 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.495 AC: 75172 AN: 151982 Hom.: 20135 Cov.: 33 AF XY: 0.494 AC XY: 36733 AN XY: 74290

African (AFR) AF: 0.720 AC: 29867 AN: 41482

American (AMR) AF: 0.436 AC: 6657 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1436 AN: 3464

East Asian (EAS) AF: 0.516 AC: 2668 AN: 5170

South Asian (SAS) AF: 0.365 AC: 1764 AN: 4828

European-Finnish (FIN) AF: 0.508 AC: 5349 AN: 10530

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26039 AN: 67934

Other (OTH) AF: 0.471 AC: 993 AN: 2110

Alfa AF: 0.439 Hom.: 2481

Bravo AF: 0.501

Asia WGS AF: 0.473 AC: 1644 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.71
DANN	Benign	0.37
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs4333136; hg19: chr4-156128049;