Genetic Variant MYB:p.Cys374Cys (chr6-135195921-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_001130173.2(MYB):c.1122C>T(p.Cys374Cys) variant causes a synonymous change. The variant allele was found at a frequency of 0.00166 in 1,614,180 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 21 hom., cov: 33)

Exomes 𝑓: 0.00090 ( 9 hom. )

Consequence

MYB
NM_001130173.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.97

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:

MYB-AS1 (HGNC:37457): (MYB antisense RNA 1)

MYB-AS1 links:

LOC105378011 (HGNC:):

LOC105378011 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 6-135195921-C-T is Benign according to our data. Variant chr6-135195921-C-T is described in ClinVar as [Benign]. Clinvar id is 786099.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00896 (1364/152312) while in subpopulation AFR AF= 0.0314 (1304/41560). AF 95% confidence interval is 0.03. There are 21 homozygotes in gnomad4. There are 630 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYB	NM_001130173.2 link	c.1122C>T	p.Cys374Cys	synonymous_variant	Exon 9 of 16	ENST00000341911.10	NP_001123645.1	P10242-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYB	ENST00000341911.10 link	c.1122C>T	p.Cys374Cys	synonymous_variant	Exon 9 of 16	1	NM_001130173.2	ENSP00000339992.5		P10242-4

Frequencies

GnomAD3 genomes

AF:

0.00895

AC:

1362

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00243

AC:

611

AN:

251398

Hom.:

AF XY:

0.00175

AC XY:

238

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0333

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000895

AC:

1309

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000777

AC XY:

565

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0297

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000737

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.00896

AC:

1364

AN:

152312

Hom.:

Cov.:

AF XY:

0.00846

AC XY:

630

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0314

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00589

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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