chr3-69739945-C-A

Position:

• chr3-69739945-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001354604.2(MITF):​c.104+244C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 152,168 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.021 (46 hom., cov: 32)
• Consequence: MITF NM_001354604.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.524

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-69739945-C-A is Benign according to our data. Variant chr3-69739945-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1197772.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0211 (3205/152168) while in subpopulation NFE AF= 0.0331 (2247/67986). AF 95% confidence interval is 0.0319. There are 46 homozygotes in gnomad4. There are 1452 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3205 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MITF	NM_001354604.2	c.104+244C>A		intron_variant		ENST00000352241.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MITF	ENST00000352241.9	c.104+244C>A		intron_variant		1	NM_001354604.2	P4

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3208 AN: 152050 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00625

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0211 AC: 3205 AN: 152168 Hom.: 46 Cov.: 32 AF XY: 0.0195 AC XY: 1452 AN XY: 74382

Gnomad4 AFR AF: 0.00623

Gnomad4 AMR AF: 0.0157

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00997

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0331

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0247 Hom.: 9

Bravo AF: 0.0213

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.7
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs45519135; hg19: chr3-69789096;