chr16-79598568-G-A

Position:

• chr16-79598568-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005360.5(MAF):​c.1118+217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,435,962 control chromosomes in the GnomAD database, including 53,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5470 hom., cov: 26)
  • Exomes 𝑓: 0.27 (48358 hom.)
• Consequence: MAF NM_005360.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-79598568-G-A is Benign according to our data. Variant chr16-79598568-G-A is described in ClinVar as [Benign]. Clinvar id is 1291603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAF	NM_005360.5	c.1118+217C>T		intron_variant		ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.1118+217C>T		intron_variant		1	NM_005360.5	ENSP00000327048	A2
MAF	ENST00000393350.1	c.*213C>T		3_prime_UTR_variant	1/1			ENSP00000377019	A2
MAF	ENST00000569649.1	c.1118+217C>T		intron_variant		5		ENSP00000455097	P4

Frequencies

GnomAD3 genomes AF: 0.269 AC: 39266 AN: 146156 Hom.: 5461 Cov.: 26

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.270 AC: 348862 AN: 1289698 Hom.: 48358 Cov.: 57 AF XY: 0.270 AC XY: 169166 AN XY: 625772

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.0135

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.269 AC: 39299 AN: 146264 Hom.: 5470 Cov.: 26 AF XY: 0.270 AC XY: 19150 AN XY: 70948

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.00930

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.255

Alfa AF: 0.266 Hom.: 1128

Bravo AF: 0.257

Asia WGS AF: 0.146 AC: 508 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.76

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: rs1046958; hg19: chr16-79632465;