chr8-143429783-ATGGTGG-A

Position:

• chr8-143429783-ATGGTGG-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_201589.4(MAFA):​c.618_623delCCACCA​(p.His207_His208del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.105 in 1,041,888 control chromosomes in the GnomAD database, including 3,246 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.059 (345 hom., cov: 0)
  • Exomes 𝑓: 0.11 (2901 hom.)
• Consequence: MAFA NM_201589.4 disruptive_inframe_deletion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.55

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 8-143429783-ATGGTGG-A is Benign according to our data. Variant chr8-143429783-ATGGTGG-A is described in ClinVar as [Benign]. Clinvar id is 3055523.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAFA	NM_201589.4	c.618_623delCCACCA	p.His207_His208del	disruptive_inframe_deletion	1/1	ENST00000333480.3	NP_963883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAFA	ENST00000333480.3	c.618_623delCCACCA	p.His207_His208del	disruptive_inframe_deletion	1/1	6	NM_201589.4	ENSP00000328364.2
MAFA	ENST00000528185.1	n.110_115delCCACCA		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 8648 AN: 146588 Hom.: 345 Cov.: 0

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.0203

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.0691

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.0743

GnomAD3 exomes AF: 0.114 AC: 7749 AN: 68082 Hom.: 142 AF XY: 0.114 AC XY: 4266 AN XY: 37262

Gnomad AFR exome AF: 0.0630

Gnomad AMR exome AF: 0.0934

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.0471

Gnomad SAS exome AF: 0.0654

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.149

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.113 AC: 101200 AN: 895184 Hom.: 2901 AF XY: 0.113 AC XY: 49285 AN XY: 436250

Gnomad4 AFR exome AF: 0.0499

Gnomad4 AMR exome AF: 0.0988

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.0199

Gnomad4 SAS exome AF: 0.0488

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.0589 AC: 8647 AN: 146704 Hom.: 345 Cov.: 0 AF XY: 0.0563 AC XY: 4023 AN XY: 71456

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.0517

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.0735

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MAFA-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 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

Splicing

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;