4-155214098-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000910.4(NPY2R):c.159C>T(p.Leu53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,613,992 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (178 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (178 hom.)
• Consequence: NPY2R NM_000910.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.364

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 4-155214098-C-T is Benign according to our data. Variant chr4-155214098-C-T is described in ClinVar as [Benign]. Clinvar id is 776026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.364 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY2R	NM_000910.4	c.159C>T	p.Leu53=	synonymous_variant	2/2	ENST00000329476.4
NPY2R	NM_001370180.1	c.159C>T	p.Leu53=	synonymous_variant	2/2
NPY2R	NM_001375470.1	c.159C>T	p.Leu53=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY2R	ENST00000329476.4	c.159C>T	p.Leu53=	synonymous_variant	2/2	1	NM_000910.4	P1
NPY2R	ENST00000506608.1	c.159C>T	p.Leu53=	synonymous_variant	2/2	1		P1
MAP9-AS1	ENST00000630664.2	n.208+39814C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3979 AN: 152132 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00644 AC: 1620 AN: 251464 Hom.: 70 AF XY: 0.00447 AC XY: 607 AN XY: 135904

Gnomad AFR exome AF: 0.0907

Gnomad AMR exome AF: 0.00309

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00276 AC: 4035 AN: 1461742 Hom.: 178 Cov.: 32 AF XY: 0.00236 AC XY: 1718 AN XY: 727172

Gnomad4 AFR exome AF: 0.0972

Gnomad4 AMR exome AF: 0.00380

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000184

Gnomad4 OTH exome AF: 0.00613

GnomAD4 genome AF: 0.0262 AC: 3983 AN: 152250 Hom.: 178 Cov.: 32 AF XY: 0.0254 AC XY: 1892 AN XY: 74446

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.00739

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0125 Hom.: 51

Bravo AF: 0.0300

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	4.1
Dann	Benign	0.69

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: rs2342674; hg19: chr4-156135250;