chr16-79599908-TGCCGCCGCCGCC-T

Variant names:

• chr16-79599908-TGCCGCCGCCGCC-T
• rs5818251
• NM_005360.5:c.-18_-7delGGCGGCGGCGGC

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_005360.5(MAF):​c.-18_-7delGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,554,540 control chromosomes in the GnomAD database, including 16 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0033 (13 hom.)
• Consequence: MAF NM_005360.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.29
• Publications: 3 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), G2P, Ambry Genetics
• 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

ENSG00000278058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant 16-79599908-TGCCGCCGCCGCC-T is Benign according to our data. Variant chr16-79599908-TGCCGCCGCCGCC-T is described in ClinVar as Likely_benign. ClinVar VariationId is 803278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	NM_005360.5	MANE Select	c.-18_-7delGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 2	NP_005351.2
	MAF	NM_001031804.3		c.-18_-7delGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 1	NP_001026974.1	O75444-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAF	ENST00000326043.5	TSL:1 MANE Select	c.-18_-7delGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 2	ENSP00000327048.4	O75444-1
	MAF	ENST00000393350.1	TSL:6	c.-18_-7delGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 1	ENSP00000377019.1	O75444-2
	ENSG00000278058	ENST00000767269.1		n.38_49delCGCCGCCGCCGC		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00244 AC: 368 AN: 150702 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.000609

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.00395

Gnomad ASJ AF: 0.00434

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00732

Gnomad FIN AF: 0.000288

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00335

Gnomad OTH AF: 0.000966

GnomAD2 exomes AF: 0.00299 AC: 584 AN: 195638 AF XY: 0.00347

Gnomad AFR exome AF: 0.000368

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.00342

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000559

Gnomad NFE exome AF: 0.00340

Gnomad OTH exome AF: 0.00323

GnomAD4 exome AF: 0.00327 AC: 4595 AN: 1403736 Hom.: 13 AF XY: 0.00345 AC XY: 2416 AN XY: 699342

African (AFR) AF: 0.000588 AC: 19 AN: 32308

American (AMR) AF: 0.00213 AC: 92 AN: 43204

Ashkenazi Jewish (ASJ) AF: 0.00323 AC: 82 AN: 25396

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37522

South Asian (SAS) AF: 0.00571 AC: 483 AN: 84542

European-Finnish (FIN) AF: 0.000706 AC: 26 AN: 36838

Middle Eastern (MID) AF: 0.00398 AC: 18 AN: 4528

European-Non Finnish (NFE) AF: 0.00339 AC: 3664 AN: 1081162

Other (OTH) AF: 0.00361 AC: 210 AN: 58236

GnomAD4 genome AF: 0.00244 AC: 368 AN: 150804 Hom.: 3 Cov.: 0 AF XY: 0.00231 AC XY: 170 AN XY: 73662

African (AFR) AF: 0.000607 AC: 25 AN: 41172

American (AMR) AF: 0.00395 AC: 60 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00434 AC: 15 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 4966

South Asian (SAS) AF: 0.00733 AC: 35 AN: 4774

European-Finnish (FIN) AF: 0.000288 AC: 3 AN: 10430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00335 AC: 226 AN: 67528

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.00196 Hom.: 4066

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cataract 21 multiple types (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3
Mutation Taster		=298/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5818251; hg19: chr16-79633805;