10-46462402-C-G

Variant names:

• chr10-46462402-C-G
• rs28691230
• NM_005972.6:c.234G>C

Variant summary

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

The NM_005972.6(NPY4R):​c.234G>C​(p.Leu78Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,611,828 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (1 hom., cov: 24)
  • Exomes 𝑓: 0.0016 (1 hom.)
• Consequence: NPY4R NM_005972.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.501

Genes affected

NPY4R (HGNC:9329): (neuropeptide Y receptor Y4) Enables pancreatic polypeptide receptor activity and peptide hormone binding activity. Involved in G protein-coupled receptor signaling pathway. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285402 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-46462402-C-G is Benign according to our data. Variant chr10-46462402-C-G is described in ClinVar as [Benign]. Clinvar id is 714452.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.501 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPY4R	NM_005972.6	c.234G>C	p.Leu78Leu	synonymous_variant	Exon 3 of 3	ENST00000374312.5	NP_005963.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPY4R	ENST00000374312.5	c.234G>C	p.Leu78Leu	synonymous_variant	Exon 3 of 3	1	NM_005972.6	ENSP00000363431.1
NPY4R	ENST00000612632.3	c.234G>C	p.Leu78Leu	synonymous_variant	Exon 2 of 2	1		ENSP00000480883.1
ENSG00000285402	ENST00000616785.1	n.254-14076C>G		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2432 AN: 151056 Hom.: 1 Cov.: 24

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00696

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00816

GnomAD3 exomes AF: 0.00472 AC: 1186 AN: 251174 Hom.: 0 AF XY: 0.00342 AC XY: 465 AN XY: 135802

Gnomad AFR exome AF: 0.0645

Gnomad AMR exome AF: 0.00399

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00162 AC: 2360 AN: 1460654 Hom.: 1 Cov.: 32 AF XY: 0.00137 AC XY: 994 AN XY: 726700

Gnomad4 AFR exome AF: 0.0590

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000459

Gnomad4 OTH exome AF: 0.00330

GnomAD4 genome AF: 0.0161 AC: 2437 AN: 151174 Hom.: 1 Cov.: 24 AF XY: 0.0152 AC XY: 1127 AN XY: 73928

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.00695

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00807

Alfa AF: 0.00337 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.3
DANN	Benign	0.60

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: rs28691230; hg19: chr10-47087017;