rs143565138

Variant names:

• chr16-79594732-G-A
• rs143565138
• NM_005360.5:c.1119-179C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-79594732-G-A
• chr16-79594732-G-C
• chr16-79594732-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001031804.3(MAF):​c.*4049C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000989 in 1,410,852 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (8 hom.)
• Consequence: MAF NM_001031804.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.562
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• cataract 21 multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-79594732-G-A is Benign according to our data. Variant chr16-79594732-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1188727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00494 (738/149394) while in subpopulation AFR AF = 0.0168 (684/40676). AF 95% confidence interval is 0.0158. There are 5 homozygotes in GnomAd4. There are 336 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031804.3. 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.1119-179C>T		intron	N/A	NP_005351.2
	MAF	NM_001031804.3		c.*4049C>T		3_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.1119-179C>T		intron	N/A	ENSP00000327048.4	O75444-1
	MAF	ENST00000393350.1	TSL:6	c.*4049C>T		3_prime_UTR	Exon 1 of 1	ENSP00000377019.1	O75444-2
	MAF	ENST00000569649.1	TSL:5	c.1118+4053C>T		intron	N/A	ENSP00000455097.1	H3BP11

Frequencies

GnomAD3 genomes AF: 0.00494 AC: 737 AN: 149318 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00287

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: 0.0000296

Gnomad OTH AF: 0.00434

GnomAD4 exome AF: 0.000521 AC: 657 AN: 1261458 Hom.: 8 Cov.: 32 AF XY: 0.000445 AC XY: 273 AN XY: 613456

African (AFR) AF: 0.0177 AC: 491 AN: 27812

American (AMR) AF: 0.00139 AC: 27 AN: 19386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18750

East Asian (EAS) AF: 0.00 AC: 0 AN: 33222

South Asian (SAS) AF: 0.0000167 AC: 1 AN: 59750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25910

Middle Eastern (MID) AF: 0.000571 AC: 2 AN: 3502

European-Non Finnish (NFE) AF: 0.0000774 AC: 79 AN: 1021244

Other (OTH) AF: 0.00110 AC: 57 AN: 51882

GnomAD4 genome AF: 0.00494 AC: 738 AN: 149394 Hom.: 5 Cov.: 32 AF XY: 0.00462 AC XY: 336 AN XY: 72700

African (AFR) AF: 0.0168 AC: 684 AN: 40676

American (AMR) AF: 0.00286 AC: 43 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67570

Other (OTH) AF: 0.00430 AC: 9 AN: 2092

Alfa AF: 0.000981 Hom.: 0

Bravo AF: 0.00626

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.37
DANN	Benign	0.71
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

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: rs143565138; hg19: chr16-79628629;