dbSNP rs3751723: IRX3:c.-235C>A (chr16-54286285-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_024336.3(IRX3):c.-235C>A variant causes a 5 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.322 in 998,464 control chromosomes in the GnomAD database, including 53,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 6817 hom., cov: 32)

Exomes 𝑓: 0.33 ( 46257 hom. )

Consequence

IRX3
NM_024336.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.27

Publications

17 publications found

Variant links:

Genes affected

IRX3 (HGNC:14360): (iroquois homeobox 3) IRX3 is a member of the Iroquois homeobox gene family (see IRX1; MIM 606197) and plays a role in an early step of neural development (Bellefroid et al., 1998 [PubMed 9427753]). Members of this family appear to play multiple roles during pattern formation of vertebrate embryos (Lewis et al., 1999 [PubMed 10370142]).[supplied by OMIM, Aug 2009]

IRX3 links:

ENSG00000287885 (HGNC:):

ENSG00000287885 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRX3	NM_024336.3 link	c.-235C>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000329734.4	NP_077312.2	P78415
IRX3	XM_005256139.4 link	c.-235C>A		5_prime_UTR_variant	Exon 1 of 4		XP_005256196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRX3	ENST00000329734.4 link	c.-235C>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_024336.3	ENSP00000331608.3		P78415

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43652

AN:

151834

Hom.:

6821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.436

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.321

GnomAD4 exome

AF:

0.328

AC:

277871

AN:

846512

Hom.:

46257

Cov.:

AF XY:

0.328

AC XY:

128618

AN XY:

392514

show subpopulations

African (AFR)

AF:

0.149

AC:

2375

AN:

15990

American (AMR)

AF:

0.318

AC:

462

AN:

1452

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

1504

AN:

5422

East Asian (EAS)

AF:

0.524

AC:

2101

AN:

4008

South Asian (SAS)

AF:

0.357

AC:

6074

AN:

17012

European-Finnish (FIN)

AF:

0.242

AC:

453

AN:

1870

Middle Eastern (MID)

AF:

0.299

AC:

502

AN:

1680

European-Non Finnish (NFE)

AF:

0.331

AC:

255123

AN:

771066

Other (OTH)

AF:

0.331

AC:

9277

AN:

28012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11659

23318

34978

46637

58296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11166

22332

33498

44664

55830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.287

AC:

43653

AN:

151952

Hom.:

6817

Cov.:

AF XY:

0.287

AC XY:

21316

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.159

AC:

6584

AN:

41534

American (AMR)

AF:

0.314

AC:

4793

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

997

AN:

3464

East Asian (EAS)

AF:

0.511

AC:

2612

AN:

5110

South Asian (SAS)

AF:

0.379

AC:

1824

AN:

4818

European-Finnish (FIN)

AF:

0.270

AC:

2855

AN:

10572

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22805

AN:

67860

Other (OTH)

AF:

0.323

AC:

681

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1579

3158

4736

6315

7894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.324

Hom.:

10497

Bravo

AF:

0.286

Asia WGS

AF:

0.452

AC:

1567

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

7.3

PromoterAI

0.15

Neutral

(source)

Mutation Taster

=294/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over