Variant chr6-135196970-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001130173.2(MYB):c.1213T>C(p.Ser405Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,612,764 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 34 hom. )

Consequence

MYB
NM_001130173.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.620

Variant links:

Genes affected

MYB (HGNC:7545): (MYB proto-oncogene, transcription factor) This gene encodes a protein with three HTH DNA-binding domains that functions as a transcription regulator. This protein plays an essential role in the regulation of hematopoiesis. This gene may be aberrently expressed or rearranged or undergo translocation in leukemias and lymphomas, and is considered to be an oncogene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

MYB links:

LOC105378011 (HGNC:):

LOC105378011 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004851252).

BP6

Variant 6-135196970-T-C is Benign according to our data. Variant chr6-135196970-T-C is described in ClinVar as [Benign]. Clinvar id is 785188.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1797/152324) while in subpopulation AFR AF= 0.0407 (1692/41576). AF 95% confidence interval is 0.0391. There are 37 homozygotes in gnomad4. There are 848 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1797 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYB	NM_001130173.2 linkuse as main transcript	c.1213T>C	p.Ser405Pro	missense_variant	10/16	ENST00000341911.10
LOC105378011	XR_001744368.2 linkuse as main transcript	n.279-970A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYB	ENST00000341911.10 linkuse as main transcript	c.1213T>C	p.Ser405Pro	missense_variant	10/16	1	NM_001130173.2	A1	P10242-4

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1794

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0407

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00295

AC:

730

AN:

247244

Hom.:

AF XY:

0.00217

AC XY:

292

AN XY:

134388

show subpopulations

Gnomad AFR exome

AF:

0.0418

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000715

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00113

AC:

1648

AN:

1460440

Hom.:

Cov.:

AF XY:

0.000957

AC XY:

695

AN XY:

726492

show subpopulations

Gnomad4 AFR exome

AF:

0.0408

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.0118

AC:

1797

AN:

152324

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

848

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0407

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.0139

ESP6500AA

AF:

0.0434

AC:

136

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00363

AC:

437

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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 submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.037

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0049

T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.029

Sift

Uncertain

0.011

D;D;D

Sift4G

Uncertain

0.052

T;T;T

Polyphen

0.74

P;.;.

Vest4

0.46

MVP

0.093

MPC

0.20

ClinPred

0.024

GERP RS

3.1

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over