4-163350687-C-T

Variant names:

• chr4-163350687-C-T
• rs77419821
• NM_006174.4:c.414C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_006174.4(NPY5R):​c.414C>T​(p.Val138Val) 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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -9 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 VariationId is 746358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.335 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006174.4. 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
	NPY5R	NM_006174.4	MANE Select	c.414C>T	p.Val138Val	synonymous	Exon 4 of 4	NP_006165.1	Q15761
	NPY5R	NM_001317091.2		c.414C>T	p.Val138Val	synonymous	Exon 4 of 4	NP_001304020.1	Q15761
	NPY5R	NM_001317092.2		c.414C>T	p.Val138Val	synonymous	Exon 5 of 5	NP_001304021.1	Q15761

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY5R	ENST00000338566.8	TSL:1 MANE Select	c.414C>T	p.Val138Val	synonymous	Exon 4 of 4	ENSP00000339377.3	Q15761
	NPY5R	ENST00000506953.1	TSL:6	c.414C>T	p.Val138Val	synonymous	Exon 1 of 1	ENSP00000423474.1	Q15761
	NPY5R	ENST00000515560.1	TSL:2	c.414C>T	p.Val138Val	synonymous	Exon 4 of 4	ENSP00000423917.1	Q15761

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

GnomAD2 exomes AF: 0.000768 AC: 193 AN: 251266 AF XY: 0.000744

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 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

African (AFR) AF: 0.000239 AC: 8 AN: 33472

American (AMR) AF: 0.000246 AC: 11 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00586 AC: 153 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86246

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53338

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00126 AC: 1396 AN: 1111748

Other (OTH) AF: 0.00103 AC: 62 AN: 60386

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

African (AFR) AF: 0.000192 AC: 8 AN: 41570

American (AMR) AF: 0.000262 AC: 4 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00101 AC: 69 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

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

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.6
DANN	Benign	0.69
PhyloP100		0.34
PromoterAI		0.0056	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs77419821; hg19: chr4-164271839;