Variant 8-143429825-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_201589.4(MAFA):c.582T>C(p.His194=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 151,106 control chromosomes in the GnomAD database, including 74,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 1.0 ( 74879 hom., cov: 28)

Exomes 𝑓: 1.0 ( 667929 hom. )

Failed GnomAD Quality Control

Consequence

MAFA
NM_201589.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0620

Variant links:

Genes affected

MAFA (HGNC:23145): (MAF bZIP transcription factor A) MAFA is a transcription factor that binds RIPE3b, a conserved enhancer element that regulates pancreatic beta cell-specific expression of the insulin gene (INS; MIM 176730) (Olbrot et al., 2002 [PubMed 12011435]).[supplied by OMIM, Mar 2008]

MAFA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 8-143429825-A-G is Benign according to our data. Variant chr8-143429825-A-G is described in ClinVar as [Benign]. Clinvar id is 3059208.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.062 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAFA	NM_201589.4 linkuse as main transcript	c.582T>C	p.His194=	synonymous_variant	1/1	ENST00000333480.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAFA	ENST00000333480.3 linkuse as main transcript	c.582T>C	p.His194=	synonymous_variant	1/1		NM_201589.4	P1
MAFA	ENST00000528185.1 linkuse as main transcript	n.74T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.996

AC:

150324

AN:

150998

Hom.:

74827

Cov.:

show subpopulations

Gnomad AFR

AF:

0.985

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

0.999

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.998

GnomAD3 exomes

AF:

0.999

AC:

93789

AN:

93910

Hom.:

46838

AF XY:

0.999

AC XY:

52354

AN XY:

52426

show subpopulations

Gnomad AFR exome

AF:

0.981

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

0.999

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.999

AC:

1337668

AN:

1339486

Hom.:

667929

Cov.:

109

AF XY:

0.999

AC XY:

657574

AN XY:

658488

show subpopulations

Gnomad4 AFR exome

AF:

0.984

Gnomad4 AMR exome

AF:

0.996

Gnomad4 ASJ exome

AF:

0.999

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.997

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.998

GnomAD4 genome

AF:

0.996

AC:

150430

AN:

151106

Hom.:

74879

Cov.:

AF XY:

0.996

AC XY:

73450

AN XY:

73774

show subpopulations

Gnomad4 AFR

AF:

0.985

Gnomad4 AMR

AF:

0.998

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

0.999

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.998

Alfa

AF:

0.998

Hom.:

12790

Asia WGS

AF:

0.998

AC:

3408

AN:

3416

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MAFA-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.3

DANN

Benign

0.52

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.

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