rs1036051

Positions:

• chr3-69850216-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354604.2(MITF):​c.105-28918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,954 control chromosomes in the GnomAD database, including 20,097 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (20097 hom., cov: 32)
• Consequence: MITF NM_001354604.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183

Genes affected

MITF (HGNC:7105): (melanocyte inducing transcription factor) The protein encoded by this gene is a transcription factor that contains both basic helix-loop-helix and leucine zipper structural features. The encoded protein regulates melanocyte development and is responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the this gene cause auditory-pigmentary syndromes, such as Waardenburg syndrome type 2 and Tietz syndrome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MITF	NM_001354604.2	c.105-28918C>T		intron_variant		ENST00000352241.9	NP_001341533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MITF	ENST00000352241.9	c.105-28918C>T		intron_variant		1	NM_001354604.2	ENSP00000295600	P4

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74675 AN: 151836 Hom.: 20084 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.529

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.492 AC: 74721 AN: 151954 Hom.: 20097 Cov.: 32 AF XY: 0.485 AC XY: 35989 AN XY: 74272

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.524

Alfa AF: 0.531 Hom.: 3839

Bravo AF: 0.470

Asia WGS AF: 0.268 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.22

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1036051; hg19: chr3-69899367;