chr7-34811812-A-G

Variant names:

• chr7-34811812-A-G
• rs325465
• NM_207172.2:c.427A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_207172.2(NPSR1):​c.427A>G​(p.Ser143Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,613,068 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00094 (24 hom.)
• Consequence: NPSR1 NM_207172.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.61
• Publications: 10 publications found

Genes affected

NPSR1 (HGNC:23631): (neuropeptide S receptor 1) This gene encodes a member of the vasopressin/oxytocin subfamily of G protein-coupled receptors. The encoded membrane protein acts as a receptor for neuropeptide S and affects a variety of cellular processes through its signaling. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. Polymorphisms in this gene have also been associated with asthma susceptibility, panic disorders, inflammatory bowel disease, and rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

NPSR1-AS1 (HGNC:22128): (NPSR1 antisense RNA 1) This gene is located within a region that has been associated with asthma susceptibility. The locus is considered non-protein-coding based on lack of protein homology and a lack of experimental support for an encoded protein. Three alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2010]

ENSG00000300889 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015120894).
• BP6: Variant 7-34811812-A-G is Benign according to our data. Variant chr7-34811812-A-G is described in ClinVar as Benign. ClinVar VariationId is 769708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00858 (1302/151726) while in subpopulation AFR AF = 0.0303 (1252/41252). AF 95% confidence interval is 0.029. There are 14 homozygotes in GnomAd4. There are 637 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207172.2. 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
	NPSR1	NM_207172.2	MANE Select	c.427A>G	p.Ser143Gly	missense	Exon 4 of 9	NP_997055.1	Q6W5P4-1
	NPSR1	NM_001300935.2		c.427A>G	p.Ser143Gly	missense	Exon 4 of 10	NP_001287864.1	Q6W5P4-3
	NPSR1	NM_207173.2		c.427A>G	p.Ser143Gly	missense	Exon 4 of 9	NP_997056.1	Q6W5P4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPSR1	ENST00000360581.6	TSL:1 MANE Select	c.427A>G	p.Ser143Gly	missense	Exon 4 of 9	ENSP00000353788.1	Q6W5P4-1
	NPSR1	ENST00000381539.3	TSL:1	c.427A>G	p.Ser143Gly	missense	Exon 4 of 10	ENSP00000370950.3	Q6W5P4-3
	NPSR1	ENST00000359791.5	TSL:1	c.427A>G	p.Ser143Gly	missense	Exon 4 of 9	ENSP00000352839.1	Q6W5P4-4

Frequencies

GnomAD3 genomes AF: 0.00854 AC: 1294 AN: 151610 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00232 AC: 582 AN: 250864 AF XY: 0.00171

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000942 AC: 1377 AN: 1461342 Hom.: 24 Cov.: 30 AF XY: 0.000847 AC XY: 616 AN XY: 727012

African (AFR) AF: 0.0309 AC: 1033 AN: 33418

American (AMR) AF: 0.00161 AC: 72 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86178

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53416

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5764

European-Non Finnish (NFE) AF: 0.000114 AC: 127 AN: 1111820

Other (OTH) AF: 0.00189 AC: 114 AN: 60350

GnomAD4 genome AF: 0.00858 AC: 1302 AN: 151726 Hom.: 14 Cov.: 32 AF XY: 0.00859 AC XY: 637 AN XY: 74148

African (AFR) AF: 0.0303 AC: 1252 AN: 41252

American (AMR) AF: 0.00262 AC: 40 AN: 15254

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10440

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.00314 Hom.: 8

Bravo AF: 0.00994

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0300 AC: 132

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00297 AC: 361

EpiCase AF: 0.000382

EpiControl AF: 0.000593

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
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.015	T
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.76
MVP		0.95
MPC		0.030
ClinPred		0.056	T
GERP RS		4.2
Varity_R		0.73
gMVP		0.83
Mutation Taster		=78/22	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: rs325465; hg19: chr7-34851424;