chr16-79594275-C-G

Variant names:

• chr16-79594275-C-G
• rs30412
• NM_005360.5:c.*185G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005360.5(MAF):​c.*185G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 614,508 control chromosomes in the GnomAD database, including 258,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (58873 hom., cov: 31)
  • Exomes 𝑓: 0.93 (199435 hom.)
• Consequence: MAF NM_005360.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0400
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-79594275-C-G is Benign according to our data. Variant chr16-79594275-C-G is described in ClinVar as [Benign]. Clinvar id is 1281348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAF	NM_005360.5	c.*185G>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000326043.5	NP_005351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAF	ENST00000326043.5	c.*185G>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_005360.5	ENSP00000327048.4
MAF	ENST00000569649.1	c.1118+4510G>C		intron_variant	Intron 1 of 1	5		ENSP00000455097.1
MAF	ENST00000393350.1	c.*4506G>C		downstream_gene_variant		6		ENSP00000377019.1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133080 AN: 151954 Hom.: 58847 Cov.: 31

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.897

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.902

GnomAD4 exome AF: 0.928 AC: 429027 AN: 462436 Hom.: 199435 Cov.: 5 AF XY: 0.930 AC XY: 228287 AN XY: 245578

African (AFR) AF: 0.738 AC: 9457 AN: 12820

American (AMR) AF: 0.962 AC: 22028 AN: 22900

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 13954 AN: 14532

East Asian (EAS) AF: 0.996 AC: 29766 AN: 29900

South Asian (SAS) AF: 0.944 AC: 43261 AN: 45816

European-Finnish (FIN) AF: 0.897 AC: 23616 AN: 26318

Middle Eastern (MID) AF: 0.949 AC: 1875 AN: 1976

European-Non Finnish (NFE) AF: 0.925 AC: 260882 AN: 282002

Other (OTH) AF: 0.924 AC: 24188 AN: 26172

GnomAD4 genome AF: 0.876 AC: 133156 AN: 152072 Hom.: 58873 Cov.: 31 AF XY: 0.879 AC XY: 65343 AN XY: 74326

African (AFR) AF: 0.736 AC: 30483 AN: 41410

American (AMR) AF: 0.946 AC: 14481 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 3347 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5151 AN: 5180

South Asian (SAS) AF: 0.946 AC: 4544 AN: 4804

European-Finnish (FIN) AF: 0.897 AC: 9493 AN: 10582

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62623 AN: 68008

Other (OTH) AF: 0.901 AC: 1902 AN: 2112

Alfa AF: 0.863 Hom.: 3314

Bravo AF: 0.874

Asia WGS AF: 0.939 AC: 3265 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs30412; hg19: chr16-79628172;