rs145460865

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021625.5(TRPV4):​c.1891+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,528,462 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 31)
Exomes 𝑓: 0.0058 ( 51 hom. )

Consequence

TRPV4
NM_021625.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0680
Variant links:
Genes affected
TRPV4 (HGNC:18083): (transient receptor potential cation channel subfamily V member 4) This gene encodes a member of the OSM9-like transient receptor potential channel (OTRPC) subfamily in the transient receptor potential (TRP) superfamily of ion channels. The encoded protein is a Ca2+-permeable, nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure. Mutations in this gene are the cause of spondylometaphyseal and metatropic dysplasia and hereditary motor and sensory neuropathy type IIC. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 12-109792316-G-A is Benign according to our data. Variant chr12-109792316-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00468 (703/150198) while in subpopulation NFE AF= 0.00706 (478/67742). AF 95% confidence interval is 0.00653. There are 3 homozygotes in gnomad4. There are 341 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 703 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRPV4NM_021625.5 linkuse as main transcriptc.1891+47C>T intron_variant ENST00000261740.7 NP_067638.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRPV4ENST00000261740.7 linkuse as main transcriptc.1891+47C>T intron_variant 1 NM_021625.5 ENSP00000261740 P1Q9HBA0-1

Frequencies

GnomAD3 genomes
AF:
0.00468
AC:
703
AN:
150146
Hom.:
3
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000933
Gnomad AMI
AF:
0.00769
Gnomad AMR
AF:
0.00166
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.000587
Gnomad SAS
AF:
0.00126
Gnomad FIN
AF:
0.0137
Gnomad MID
AF:
0.00321
Gnomad NFE
AF:
0.00706
Gnomad OTH
AF:
0.00290
GnomAD3 exomes
AF:
0.00585
AC:
1451
AN:
248022
Hom.:
12
AF XY:
0.00589
AC XY:
792
AN XY:
134486
show subpopulations
Gnomad AFR exome
AF:
0.000635
Gnomad AMR exome
AF:
0.00213
Gnomad ASJ exome
AF:
0.000301
Gnomad EAS exome
AF:
0.000328
Gnomad SAS exome
AF:
0.00191
Gnomad FIN exome
AF:
0.0114
Gnomad NFE exome
AF:
0.00914
Gnomad OTH exome
AF:
0.00577
GnomAD4 exome
AF:
0.00576
AC:
7944
AN:
1378264
Hom.:
51
Cov.:
26
AF XY:
0.00569
AC XY:
3921
AN XY:
689254
show subpopulations
Gnomad4 AFR exome
AF:
0.000887
Gnomad4 AMR exome
AF:
0.00223
Gnomad4 ASJ exome
AF:
0.000198
Gnomad4 EAS exome
AF:
0.000235
Gnomad4 SAS exome
AF:
0.00187
Gnomad4 FIN exome
AF:
0.0115
Gnomad4 NFE exome
AF:
0.00646
Gnomad4 OTH exome
AF:
0.00522
GnomAD4 genome
AF:
0.00468
AC:
703
AN:
150198
Hom.:
3
Cov.:
31
AF XY:
0.00466
AC XY:
341
AN XY:
73188
show subpopulations
Gnomad4 AFR
AF:
0.000931
Gnomad4 AMR
AF:
0.00166
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.000589
Gnomad4 SAS
AF:
0.00126
Gnomad4 FIN
AF:
0.0137
Gnomad4 NFE
AF:
0.00706
Gnomad4 OTH
AF:
0.00287
Alfa
AF:
0.00488
Hom.:
1
Bravo
AF:
0.00373
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 27, 2018- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
9.2
DANN
Benign
0.42

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: rs145460865; hg19: chr12-110230121; API