8-143429783-ATGGTGGTGGTGGTGGTGG-ATGGTGGTGGTGGTGG

Variant names:

• chr8-143429783-ATGG-A
• rs141816879
• NM_201589.4:c.621_623delCCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_201589.4(MAFA):​c.621_623delCCA​(p.His208del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,409,010 control chromosomes in the GnomAD database, including 389,479 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.89 (58895 hom., cov: 0)
  • Exomes 𝑓: 0.76 (330584 hom.)
• Consequence: MAFA NM_201589.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAFA	NM_201589.4	c.621_623delCCA	p.His208del	disruptive_inframe_deletion	Exon 1 of 1	ENST00000333480.3	NP_963883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAFA	ENST00000333480.3	c.621_623delCCA	p.His208del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_201589.4	ENSP00000328364.2
MAFA	ENST00000528185.1	n.113_115delCCA		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.893 AC: 131244 AN: 146896 Hom.: 58843 Cov.: 0

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.888

GnomAD3 exomes AF: 0.872 AC: 59358 AN: 68082 Hom.: 25605 AF XY: 0.872 AC XY: 32485 AN XY: 37262

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.949

Gnomad SAS exome AF: 0.930

Gnomad FIN exome AF: 0.872

Gnomad NFE exome AF: 0.845

Gnomad OTH exome AF: 0.863

GnomAD4 exome AF: 0.758 AC: 956618 AN: 1261994 Hom.: 330584 AF XY: 0.756 AC XY: 469176 AN XY: 620308

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.761

Gnomad4 ASJ exome AF: 0.717

Gnomad4 EAS exome AF: 0.774

Gnomad4 SAS exome AF: 0.765

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.747

GnomAD4 genome AF: 0.893 AC: 131354 AN: 147016 Hom.: 58895 Cov.: 0 AF XY: 0.897 AC XY: 64219 AN XY: 71630

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.981

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs141816879; hg19: chr8-144511953;