rs113182184

chr6-135200357-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001130173.2(MYB):c.1892G>A(p.Gly631Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,614,076 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: MYB NM_001130173.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.30

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]

LOC105378011 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0075646937).
• BP6: Variant 6-135200357-G-A is Benign according to our data. Variant chr6-135200357-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 238 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYB	NM_001130173.2	c.1892G>A	p.Gly631Glu	missense_variant	13/16	ENST00000341911.10
LOC105378011	XR_001744368.2	n.279-4357C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYB	ENST00000341911.10	c.1892G>A	p.Gly631Glu	missense_variant	13/16	1	NM_001130173.2	A1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 238 AN: 152114 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00526

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

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: 0.00

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000287 AC: 72 AN: 250894 Hom.: 0 AF XY: 0.000162 AC XY: 22 AN XY: 135590

Gnomad AFR exome AF: 0.00382

Gnomad AMR exome AF: 0.000145

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: 0.00000883

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000178 AC: 260 AN: 1461844 Hom.: 2 Cov.: 31 AF XY: 0.000149 AC XY: 108 AN XY: 727218

Gnomad4 AFR exome AF: 0.00633

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.00155 AC: 236 AN: 152232 Hom.: 1 Cov.: 33 AF XY: 0.00155 AC XY: 115 AN XY: 74416

Gnomad4 AFR AF: 0.00522

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000335 Hom.: 0

Bravo AF: 0.00176

ESP6500AA AF: 0.00613 AC: 27

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000362 AC: 44

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MYB-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;T;T;.;T;T;.;.;.;.;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0076	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.96	D;D;D;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.55	T
Sift4G	Benign	0.46	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.99	D;P;.;.;D;B;.;.;.;.;.;.
Vest4		0.18
MVP		0.20
MPC		0.21
ClinPred		0.032	T
GERP RS		3.0
Varity_R		0.092
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs113182184; hg19: chr6-135521495; COSMIC: COSV57201233; COSMIC: COSV57201233;