rs28691230

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-46462402-C-G
• chr10-46462402-C-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

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
• Publications: 1 publications found

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:):

LINC00842 (HGNC:44989): (long intergenic non-protein coding RNA 842)

ACMG classification

Our verdict: Benign. The variant received -7 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 VariationId is 714452.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.501 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005972.6. 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
	NPY4R	NM_005972.6	MANE Select	c.234G>C	p.Leu78Leu	synonymous	Exon 3 of 3	NP_005963.4
	NPY4R	NM_001278794.2		c.234G>C	p.Leu78Leu	synonymous	Exon 2 of 2	NP_001265723.1	P50391

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPY4R	ENST00000374312.5	TSL:1 MANE Select	c.234G>C	p.Leu78Leu	synonymous	Exon 3 of 3	ENSP00000363431.1	P50391
	NPY4R	ENST00000612632.3	TSL:1	c.234G>C	p.Leu78Leu	synonymous	Exon 2 of 2	ENSP00000480883.1	P50391
	NPY4R	ENST00000908575.1		c.234G>C	p.Leu78Leu	synonymous	Exon 2 of 2	ENSP00000578634.1

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

GnomAD2 exomes AF: 0.00472 AC: 1186 AN: 251174 AF XY: 0.00342

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0590 AC: 1922 AN: 32578

American (AMR) AF: 0.00405 AC: 181 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1111892

Other (OTH) AF: 0.00330 AC: 199 AN: 60268

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0569 AC: 2307 AN: 40516

American (AMR) AF: 0.00695 AC: 106 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00807 AC: 17 AN: 2106

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00337 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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	-0.64
CADD	Benign	4.3
DANN	Benign	0.60
PhyloP100		0.50

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: rs28691230; hg19: chr10-47087017;