chr3-69763752-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001354604.2(MITF):​c.104+24051C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,358,386 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 140 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 92 hom. )

Consequence

MITF
NM_001354604.2 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.512
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 3-69763752-C-T is Benign according to our data. Variant chr3-69763752-C-T is described in ClinVar as [Benign]. Clinvar id is 1291113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0773 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MITFNM_001354604.2 linkuse as main transcriptc.104+24051C>T intron_variant ENST00000352241.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MITFENST00000352241.9 linkuse as main transcriptc.104+24051C>T intron_variant 1 NM_001354604.2 P4O75030-1

Frequencies

GnomAD3 genomes
AF:
0.0227
AC:
3461
AN:
152198
Hom.:
139
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0796
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00772
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.0129
GnomAD4 exome
AF:
0.00214
AC:
2582
AN:
1206070
Hom.:
92
Cov.:
31
AF XY:
0.00191
AC XY:
1127
AN XY:
589146
show subpopulations
Gnomad4 AFR exome
AF:
0.0814
Gnomad4 AMR exome
AF:
0.00409
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000314
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000667
Gnomad4 OTH exome
AF:
0.00506
GnomAD4 genome
AF:
0.0228
AC:
3470
AN:
152316
Hom.:
140
Cov.:
33
AF XY:
0.0223
AC XY:
1664
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0796
Gnomad4 AMR
AF:
0.00771
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.0164
Hom.:
6
Bravo
AF:
0.0262
Asia WGS
AF:
0.00346
AC:
13
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.4
DANN
Benign
0.47

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs72950039; hg19: chr3-69812903; API