Genetic Variant NM_201589.4:c.612_623delCCACCACCACCA (chr8-143429783-ATGGTGGTGGTGG-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_201589.4(MAFA):c.612_623delCCACCACCACCA(p.His205_His208del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000369 in 1,409,406 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000039 ( 1 hom. )

Consequence

MAFA
NM_201589.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.55

Publications

12 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 49 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201589.4. 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
	MAFA	NM_201589.4	MANE Select	c.612_623delCCACCACCACCA	p.His205_His208del	disruptive_inframe_deletion	Exon 1 of 1	NP_963883.2	Q8NHW3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAFA	ENST00000333480.3	TSL:6 MANE Select	c.612_623delCCACCACCACCA	p.His205_His208del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000328364.2	Q8NHW3
	MAFA	ENST00000528185.1	TSL:3	n.104_115delCCACCACCACCA		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000204

AC:

AN:

146950

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000451

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000118

AC:

AN:

68082

AF XY:

0.000188

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000222

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000153

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000388

AC:

AN:

1262456

Hom.:

AF XY:

0.0000467

AC XY:

AN XY:

620536

show subpopulations

African (AFR)

AF:

0.0000367

AC:

AN:

27250

American (AMR)

AF:

0.00

AC:

AN:

30286

Ashkenazi Jewish (ASJ)

AF:

0.0000888

AC:

AN:

22526

East Asian (EAS)

AF:

0.000170

AC:

AN:

29398

South Asian (SAS)

AF:

0.000158

AC:

AN:

69598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3710

European-Non Finnish (NFE)

AF:

0.0000291

AC:

AN:

996550

Other (OTH)

AF:

0.0000190

AC:

AN:

52622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000204

AC:

AN:

146950

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

71550

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39914

American (AMR)

AF:

0.00

AC:

AN:

14904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

4648

South Asian (SAS)

AF:

0.00

AC:

AN:

4522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000451

AC:

AN:

66480

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000745

Hom.:

4374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.5

Mutation Taster

=124/76

polymorphism

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over