rs1229626204

Variant names:

• chr16-79599192-CCCGCCGCCTCCGCCG-C
• rs1229626204
• NM_005360.5:c.696_710delCGGCGGAGGCGGCGG

Your query was ambiguous. Multiple possible variants found:

• chr16-79599192-CCCGCCGCCTCCGCCG-C
• chr16-79599192-CCCGCCGCCTCCGCCG-CCCGCCGCCTCCGCCGCCGCCGCCTCCGCCG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BP6_Very_Strong

The NM_005360.5(MAF):​c.696_710delCGGCGGAGGCGGCGG​(p.Gly233_Gly237del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,026,632 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. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G232G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 29)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: MAF NM_005360.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.65
• Publications: 1 publications found

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]

MAF Gene-Disease associations (from GenCC):

• Ayme-Gripp syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• cataract 21 multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics
• cataract - microcornea syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cerulean cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pulverulent cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fine-Lubinsky syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005360.5
• BP6: Variant 16-79599192-CCCGCCGCCTCCGCCG-C is Benign according to our data. Variant chr16-79599192-CCCGCCGCCTCCGCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 474937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005360.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	NM_005360.5	MANE Select	c.696_710delCGGCGGAGGCGGCGG	p.Gly233_Gly237del	disruptive_inframe_deletion	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.696_710delCGGCGGAGGCGGCGG	p.Gly233_Gly237del	disruptive_inframe_deletion	Exon 1 of 1	NP_001026974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	ENST00000326043.5	TSL:1 MANE Select	c.696_710delCGGCGGAGGCGGCGG	p.Gly233_Gly237del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000327048.4
	MAF	ENST00000569649.1	TSL:5	c.696_710delCGGCGGAGGCGGCGG	p.Gly233_Gly237del	disruptive_inframe_deletion	Exon 1 of 2	ENSP00000455097.1
	MAF	ENST00000393350.1	TSL:6	c.696_710delCGGCGGAGGCGGCGG	p.Gly233_Gly237del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 228 AN: 145688 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.00538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000409

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: 0.0000152

Gnomad OTH AF: 0.000995

GnomAD4 exome AF: 0.000108 AC: 95 AN: 880906 Hom.: 0 AF XY: 0.0000976 AC XY: 40 AN XY: 409964

African (AFR) AF: 0.00510 AC: 87 AN: 17056

American (AMR) AF: 0.00 AC: 0 AN: 2486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6744

East Asian (EAS) AF: 0.00 AC: 0 AN: 8342

South Asian (SAS) AF: 0.00 AC: 0 AN: 17684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1856

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 791320

Other (OTH) AF: 0.000264 AC: 8 AN: 30334

GnomAD4 genome AF: 0.00159 AC: 231 AN: 145726 Hom.: 1 Cov.: 29 AF XY: 0.00164 AC XY: 116 AN XY: 70822

African (AFR) AF: 0.00545 AC: 222 AN: 40766

American (AMR) AF: 0.000408 AC: 6 AN: 14692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4948

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65722

Other (OTH) AF: 0.000987 AC: 2 AN: 2026

Alfa AF: 0.000927 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ayme-Gripp syndrome;C1857768:Cataract 21 multiple types Benign:1

Aug 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inborn genetic diseases Benign:1

Apr 20, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAF: BS1

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=158/42	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1229626204; hg19: chr16-79633089;