Genetic Variant IRX6:c.45+78A>T (chr16-55325214-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024335.3(IRX6):c.45+78A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,392,596 control chromosomes in the GnomAD database, including 408,772 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 0.77 ( 44943 hom., cov: 28)

Exomes 𝑓: 0.76 ( 363829 hom. )

Consequence

IRX6
NM_024335.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.362

Publications

6 publications found

Variant links:

Genes affected

IRX6 (HGNC:14675): (iroquois homeobox 6) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor 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, DNA-templated. Predicted to act upstream of or within detection of visible light; negative regulation of transcription, DNA-templated; and retina morphogenesis in camera-type eye. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

IRX6 links:

ENSG00000283423 (HGNC:):

ENSG00000283423 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX6	NM_024335.3	MANE Select	c.45+78A>T		intron	N/A	NP_077311.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRX6	ENST00000290552.8	TSL:1 MANE Select	c.45+78A>T	intron	N/A	ENSP00000290552.8	P78412
IRX6	ENST00000944938.1		c.45+78A>T	intron	N/A	ENSP00000614997.1
IRX6	ENST00000869145.1		c.45+78A>T	intron	N/A	ENSP00000539204.1

Frequencies

GnomAD3 genomes

AF:

0.769

AC:

116519

AN:

151578

Hom.:

44907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.793

Gnomad ASJ

AF:

0.719

Gnomad EAS

AF:

0.884

Gnomad SAS

AF:

0.845

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.701

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.751

GnomAD4 exome

AF:

0.764

AC:

948468

AN:

1240900

Hom.:

363829

AF XY:

0.766

AC XY:

479825

AN XY:

626518

show subpopulations

African (AFR)

AF:

0.782

AC:

22939

AN:

29348

American (AMR)

AF:

0.846

AC:

34950

AN:

41298

Ashkenazi Jewish (ASJ)

AF:

0.731

AC:

17852

AN:

24434

East Asian (EAS)

AF:

0.888

AC:

34024

AN:

38322

South Asian (SAS)

AF:

0.837

AC:

67389

AN:

80556

European-Finnish (FIN)

AF:

0.760

AC:

35655

AN:

46932

Middle Eastern (MID)

AF:

0.680

AC:

3665

AN:

5388

European-Non Finnish (NFE)

AF:

0.750

AC:

691524

AN:

921510

Other (OTH)

AF:

0.762

AC:

40470

AN:

53112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10869

21738

32607

43476

54345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15712

31424

47136

62848

78560

<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:

0.769

AC:

116611

AN:

151696

Hom.:

44943

Cov.:

AF XY:

0.771

AC XY:

57151

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.787

AC:

32581

AN:

41394

American (AMR)

AF:

0.794

AC:

12106

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

2494

AN:

3470

East Asian (EAS)

AF:

0.884

AC:

4456

AN:

5040

South Asian (SAS)

AF:

0.845

AC:

4046

AN:

4790

European-Finnish (FIN)

AF:

0.767

AC:

8084

AN:

10534

Middle Eastern (MID)

AF:

0.699

AC:

204

AN:

292

European-Non Finnish (NFE)

AF:

0.743

AC:

50453

AN:

67916

Other (OTH)

AF:

0.754

AC:

1581

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1280

2560

3841

5121

6401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.698

Hom.:

2343

Bravo

AF:

0.770

Asia WGS

AF:

0.878

AC:

3054

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.1

(source)

DANN

Benign

0.64

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over