4-155212560-C-T

Position:

• chr4-155212560-C-T

Variant summary

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

The NM_000910.4(NPY2R):​c.-48-1332C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,012 control chromosomes in the GnomAD database, including 1,619 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 0.14 (1619 hom., cov: 32)
• Consequence: NPY2R NM_000910.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.68

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPY2R	NM_000910.4	c.-48-1332C>T		intron_variant		ENST00000329476.4	NP_000901.1
NPY2R	NM_001370180.1	c.-48-1332C>T		intron_variant			NP_001357109.1
NPY2R	NM_001375470.1	c.-48-1332C>T		intron_variant			NP_001362399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPY2R	ENST00000329476.4	c.-48-1332C>T		intron_variant		1	NM_000910.4	ENSP00000332591	P1
NPY2R	ENST00000506608.1	c.-48-1332C>T		intron_variant		1		ENSP00000426366	P1
MAP9-AS1	ENST00000630664.2	n.208+38276C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21295 AN: 151894 Hom.: 1617 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.140 AC: 21297 AN: 152012 Hom.: 1619 Cov.: 32 AF XY: 0.144 AC XY: 10671 AN XY: 74274

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0816

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0584

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.118

Alfa AF: 0.131 Hom.: 1290

Bravo AF: 0.128

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.54

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: rs1574175; hg19: chr4-156133712; COSMIC: COSV61528257; COSMIC: COSV61528257;