Menu
GeneBe

5-1878326-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_016358.3(IRX4):c.1203G>A(p.Ala401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 1,558,380 control chromosomes in the GnomAD database, including 7,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1612 hom., cov: 34)
Exomes 𝑓: 0.087 ( 6015 hom. )

Consequence

IRX4
NM_016358.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter P:1B:1

Conservation

PhyloP100: -2.70
Variant links:
Genes affected
IRX4 (HGNC:6129): (iroquois homeobox 4) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell development; neuron differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within heart development. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-1878326-C-T is Benign according to our data. Variant chr5-1878326-C-T is described in ClinVar as [Benign]. Clinvar id is 1247023.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.7 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRX4NM_016358.3 linkuse as main transcriptc.1203G>A p.Ala401= synonymous_variant 5/5 ENST00000231357.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRX4ENST00000231357.7 linkuse as main transcriptc.1203G>A p.Ala401= synonymous_variant 5/51 NM_016358.3 P1P78413-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.122
AC:
18597
AN:
152116
Hom.:
1607
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.237
Gnomad AMI
AF:
0.0538
Gnomad AMR
AF:
0.0772
Gnomad ASJ
AF:
0.116
Gnomad EAS
AF:
0.00385
Gnomad SAS
AF:
0.0600
Gnomad FIN
AF:
0.0626
Gnomad MID
AF:
0.102
Gnomad NFE
AF:
0.0869
Gnomad OTH
AF:
0.111
GnomAD3 exomes
AF:
0.0813
AC:
13068
AN:
160656
Hom.:
715
AF XY:
0.0804
AC XY:
7030
AN XY:
87396
show subpopulations
Gnomad AFR exome
AF:
0.246
Gnomad AMR exome
AF:
0.0518
Gnomad ASJ exome
AF:
0.113
Gnomad EAS exome
AF:
0.00254
Gnomad SAS exome
AF:
0.0670
Gnomad FIN exome
AF:
0.0699
Gnomad NFE exome
AF:
0.0900
Gnomad OTH exome
AF:
0.0843
GnomAD4 exome
AF:
0.0871
AC:
122428
AN:
1406146
Hom.:
6015
Cov.:
33
AF XY:
0.0860
AC XY:
59731
AN XY:
694594
show subpopulations
Gnomad4 AFR exome
AF:
0.249
Gnomad4 AMR exome
AF:
0.0545
Gnomad4 ASJ exome
AF:
0.108
Gnomad4 EAS exome
AF:
0.00105
Gnomad4 SAS exome
AF:
0.0653
Gnomad4 FIN exome
AF:
0.0682
Gnomad4 NFE exome
AF:
0.0877
Gnomad4 OTH exome
AF:
0.0933
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.122
AC:
18630
AN:
152234
Hom.:
1612
Cov.:
34
AF XY:
0.119
AC XY:
8846
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.237
Gnomad4 AMR
AF:
0.0772
Gnomad4 ASJ
AF:
0.116
Gnomad4 EAS
AF:
0.00386
Gnomad4 SAS
AF:
0.0601
Gnomad4 FIN
AF:
0.0626
Gnomad4 NFE
AF:
0.0869
Gnomad4 OTH
AF:
0.111
Alfa
AF:
0.0963
Hom.:
355
Bravo
AF:
0.130
Asia WGS
AF:
0.0470
AC:
164
AN:
3478

ClinVar

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

Submissions by phenotype

See cases Pathogenic:1
Pathogenic, no assertion criteria providedcase-controlCytogenetics- Mohapatra Lab, Banaras Hindu University-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxOct 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.14
Dann
Benign
0.78

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: rs1689717; hg19: chr5-1878440; COSMIC: COSV51475249; COSMIC: COSV51475249; API