4-163350687-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_006174.4(NPY5R):c.414C>T(p.Val138=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,798 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: NPY5R NM_006174.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.335

Genes affected

NPY5R (HGNC:7958): (neuropeptide Y receptor Y5) The protein encoded by this gene is a receptor for neuropeptide Y and peptide YY. The encoded protein appears to be involved in regulating food intake, with defects in this gene being associated with eating disorders. Also, the encoded protein is involved in a pathway that protects neuroblastoma cells from chemotherapy-induced cell death, providing a possible therapeutic target against neuroblastoma. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 4-163350687-C-T is Benign according to our data. Variant chr4-163350687-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 746358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.335 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPY5R	NM_006174.4	c.414C>T	p.Val138=	synonymous_variant	4/4	ENST00000338566.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPY5R	ENST00000338566.8	c.414C>T	p.Val138=	synonymous_variant	4/4	1	NM_006174.4	P1
NPY5R	ENST00000506953.1	c.414C>T	p.Val138=	synonymous_variant	1/1			P1
NPY5R	ENST00000515560.1	c.414C>T	p.Val138=	synonymous_variant	4/4	2		P1

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000768 AC: 193 AN: 251266 Hom.: 0 AF XY: 0.000744 AC XY: 101 AN XY: 135790

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00556

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.000915

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00114 AC: 1672 AN: 1461506 Hom.: 2 Cov.: 33 AF XY: 0.00115 AC XY: 839 AN XY: 727078

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00586

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.000244

Gnomad4 NFE exome AF: 0.00126

Gnomad4 OTH exome AF: 0.00103

GnomAD4 genome AF: 0.000650 AC: 99 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.000631 AC XY: 47 AN XY: 74452

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000747 Hom.: 0

Bravo AF: 0.000665

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	8.6
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: rs77419821; hg19: chr4-164271839;