Genetic Variant XM_024450279.2:c.*28+34756G>A (chr16-79551124-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

-12

BP4_StrongBA1

The XM_024450279.2(MAF):c.*28+34756G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,082 control chromosomes in the GnomAD database, including 59,429 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 0.88 ( 59429 hom., cov: 30)

Consequence

MAF
XM_024450279.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00200

Publications

7 publications found

Variant links:

Genes affected

MAF (HGNC:6776): (MAF bZIP transcription factor) The protein encoded by this gene is a DNA-binding, leucine zipper-containing transcription factor that acts as a homodimer or as a heterodimer. Depending on the binding site and binding partner, the encoded protein can be a transcriptional activator or repressor. This protein plays a role in the regulation of several cellular processes, including embryonic lens fiber cell development, increased T-cell susceptibility to apoptosis, and chondrocyte terminal differentiation. Defects in this gene are a cause of juvenile-onset pulverulent cataract as well as congenital cerulean cataract 4 (CCA4). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

MAF Gene-Disease associations (from GenCC):

Ayme-Gripp syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
cataract 21 multiple types
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
cataract - microcornea syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cerulean cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pulverulent cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Fine-Lubinsky syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MAF links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
MAF	XM_024450279.2 link	c.*28+34756G>A	intron_variant	Intron 2 of 2	XP_024306047.1
MAF	XR_001751902.3 link	n.2015+34756G>A	intron_variant	Intron 2 of 3
MAF	XR_002957802.2 link	n.2015+34756G>A	intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes

AF:

0.881

AC:

133831

AN:

151964

Hom.:

59393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.763

Gnomad AMI

AF:

0.962

Gnomad AMR

AF:

0.914

Gnomad ASJ

AF:

0.912

Gnomad EAS

AF:

0.866

Gnomad SAS

AF:

0.920

Gnomad FIN

AF:

0.968

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.926

Gnomad OTH

AF:

0.895

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.881

AC:

133918

AN:

152082

Hom.:

59429

Cov.:

AF XY:

0.883

AC XY:

65659

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.763

AC:

31598

AN:

41436

American (AMR)

AF:

0.914

AC:

13977

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.912

AC:

3165

AN:

3472

East Asian (EAS)

AF:

0.866

AC:

4450

AN:

5138

South Asian (SAS)

AF:

0.920

AC:

4424

AN:

4808

European-Finnish (FIN)

AF:

0.968

AC:

10274

AN:

10616

Middle Eastern (MID)

AF:

0.922

AC:

271

AN:

294

European-Non Finnish (NFE)

AF:

0.926

AC:

62994

AN:

68004

Other (OTH)

AF:

0.896

AC:

1890

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

762

1524

2286

3048

3810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.912

Hom.:

239970

Bravo

AF:

0.869

Asia WGS

AF:

0.871

AC:

3027

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.66

(source)

DANN

Benign

0.34

PhyloP100

-0.0020

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over