9-100104623-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014425.5(INVS):​c.102C>T​(p.Ile34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000999 in 1,607,312 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00057 ( 11 hom. )

Consequence

INVS
NM_014425.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.00
Variant links:
Genes affected
INVS (HGNC:17870): (inversin) This gene encodes a protein containing multiple ankyrin domains and two IQ calmodulin-binding domains. The encoded protein may function in renal tubular development and function, and in left-right axis determination. This protein interacts with nephrocystin and infers a connection between primary cilia function and left-right axis determination. A similar protein in mice interacts with calmodulin. Mutations in this gene have been associated with nephronophthisis type 2. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 9-100104623-C-T is Benign according to our data. Variant chr9-100104623-C-T is described in ClinVar as [Benign]. Clinvar id is 167194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00512 (780/152232) while in subpopulation AFR AF= 0.0178 (740/41546). AF 95% confidence interval is 0.0167. There are 2 homozygotes in gnomad4. There are 351 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
INVSNM_014425.5 linkuse as main transcriptc.102C>T p.Ile34= synonymous_variant 2/17 ENST00000262457.7 NP_055240.2
INVSNM_001318381.2 linkuse as main transcriptc.-275C>T 5_prime_UTR_variant 2/18 NP_001305310.1
INVSNM_001318382.2 linkuse as main transcriptc.-888C>T 5_prime_UTR_variant 2/17 NP_001305311.1
INVSNR_134606.2 linkuse as main transcriptn.300C>T non_coding_transcript_exon_variant 2/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
INVSENST00000262457.7 linkuse as main transcriptc.102C>T p.Ile34= synonymous_variant 2/171 NM_014425.5 ENSP00000262457 A2Q9Y283-1

Frequencies

GnomAD3 genomes
AF:
0.00511
AC:
778
AN:
152114
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0178
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00148
AC:
371
AN:
251412
Hom.:
1
AF XY:
0.00110
AC XY:
150
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.0203
Gnomad AMR exome
AF:
0.000838
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:
0.0000967
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000567
AC:
825
AN:
1455080
Hom.:
11
Cov.:
28
AF XY:
0.000490
AC XY:
355
AN XY:
724296
show subpopulations
Gnomad4 AFR exome
AF:
0.0180
Gnomad4 AMR exome
AF:
0.000895
Gnomad4 ASJ exome
AF:
0.0000767
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000968
Gnomad4 OTH exome
AF:
0.00111
GnomAD4 genome
AF:
0.00512
AC:
780
AN:
152232
Hom.:
2
Cov.:
32
AF XY:
0.00472
AC XY:
351
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0178
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00320
Hom.:
3
Bravo
AF:
0.00625
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of ChicagoAug 15, 2022- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Apr 17, 2014- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Nephronophthisis Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
9.3
DANN
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs115640267; hg19: chr9-102866905; API