Genetic Variant MAF:p.His187del (chr16-79599341-CGTG-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The NM_005360.5(MAF):c.559_561delCAC(p.His187del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 970,024 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

MAF
NM_005360.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 3.52

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_005360.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 16-79599341-CGTG-C is Benign according to our data. Variant chr16-79599341-CGTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 376806.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 176 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5 link	c.559_561delCAC	p.His187del	conservative_inframe_deletion	Exon 1 of 2	ENST00000326043.5	NP_005351.2	O75444-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAF	ENST00000326043.5 link	c.559_561delCAC	p.His187del	conservative_inframe_deletion	Exon 1 of 2	1	NM_005360.5	ENSP00000327048.4	O75444-1
MAF	ENST00000569649.1 link	c.559_561delCAC	p.His187del	conservative_inframe_deletion	Exon 1 of 2	5		ENSP00000455097.1	H3BP11
MAF	ENST00000393350.1 link	c.559_561delCAC	p.His187del	conservative_inframe_deletion	Exon 1 of 1	6		ENSP00000377019.1	O75444-2

Frequencies

GnomAD3 genomes

AF:

0.00000687

AC:

AN:

145488

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000121

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000213

AC:

176

AN:

824536

Hom.:

AF XY:

0.000209

AC XY:

AN XY:

382048

show subpopulations

Gnomad4 AFR exome

AF:

0.000257

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.000190

Gnomad4 EAS exome

AF:

0.00181

Gnomad4 SAS exome

AF:

0.000295

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.000193

Gnomad4 OTH exome

AF:

0.000330

GnomAD4 genome

AF:

0.00000687

AC:

AN:

145488

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70676

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000121

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 15, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MAF-related disorder

Benign:1

Dec 01, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

16-79599341-CGTGGTGGTG-CGTGGTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over