chr7-34778526-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_207172.2(NPSR1):​c.345G>A​(p.Thr115=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00151 in 1,612,876 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00088 ( 22 hom. )

Consequence

NPSR1
NM_207172.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.42
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP6
Variant 7-34778526-G-A is Benign according to our data. Variant chr7-34778526-G-A is described in ClinVar as [Benign]. Clinvar id is 792072.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0076 (1157/152194) while in subpopulation AFR AF= 0.0267 (1109/41512). AF 95% confidence interval is 0.0254. There are 11 homozygotes in gnomad4. There are 571 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPSR1NM_207172.2 linkuse as main transcriptc.345G>A p.Thr115= synonymous_variant 3/9 ENST00000360581.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPSR1ENST00000360581.6 linkuse as main transcriptc.345G>A p.Thr115= synonymous_variant 3/91 NM_207172.2 P1Q6W5P4-1

Frequencies

GnomAD3 genomes
AF:
0.00758
AC:
1153
AN:
152078
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0267
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00242
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:
0.0000735
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00216
AC:
542
AN:
250636
Hom.:
7
AF XY:
0.00165
AC XY:
224
AN XY:
135484
show subpopulations
Gnomad AFR exome
AF:
0.0281
Gnomad AMR exome
AF:
0.00154
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000203
Gnomad OTH exome
AF:
0.000656
GnomAD4 exome
AF:
0.000878
AC:
1282
AN:
1460682
Hom.:
22
Cov.:
30
AF XY:
0.000798
AC XY:
580
AN XY:
726670
show subpopulations
Gnomad4 AFR exome
AF:
0.0278
Gnomad4 AMR exome
AF:
0.00152
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000130
Gnomad4 OTH exome
AF:
0.00167
GnomAD4 genome
AF:
0.00760
AC:
1157
AN:
152194
Hom.:
11
Cov.:
32
AF XY:
0.00767
AC XY:
571
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.0267
Gnomad4 AMR
AF:
0.00242
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:
0.00284
Alfa
AF:
0.00499
Hom.:
3
Bravo
AF:
0.00890
Asia WGS
AF:
0.00231
AC:
9
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000654

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.22
CADD
Benign
13
DANN
Benign
0.84

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs324982; hg19: chr7-34818138; API