rs78356356

Positions:

• chr3-69774942-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001354604.2(MITF):​c.104+35241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 152,196 control chromosomes in the GnomAD database, including 105 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 0.030 (105 hom., cov: 32)
• Consequence: MITF NM_001354604.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0296 (4507/152196) while in subpopulation NFE AF= 0.0393 (2669/67996). AF 95% confidence interval is 0.038. There are 105 homozygotes in gnomad4. There are 2310 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4507 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MITF	NM_001354604.2	c.104+35241A>G		intron_variant		ENST00000352241.9	NP_001341533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MITF	ENST00000352241.9	c.104+35241A>G		intron_variant		1	NM_001354604.2	ENSP00000295600	P4

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4506 AN: 152078 Hom.: 105 Cov.: 32

Gnomad AFR AF: 0.00674

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0296 AC: 4507 AN: 152196 Hom.: 105 Cov.: 32 AF XY: 0.0311 AC XY: 2310 AN XY: 74394

Gnomad4 AFR AF: 0.00672

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0826

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0355 Hom.: 17

Bravo AF: 0.0248

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78356356; hg19: chr3-69824093;