rs73555746

Variant names:

• chr6-135200351-A-C
• rs73555746
• NM_001130173.2:c.1886A>C
• MYB p.Glu629Ala

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001130173.2(MYB):​c.1886A>C​(p.Glu629Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,614,140 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: MYB NM_001130173.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 8.37
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054531693).
• BP6: Variant 6-135200351-A-C is Benign according to our data. Variant chr6-135200351-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3035642.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 293 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130173.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYB	NM_001130173.2	MANE Select	c.1886A>C	p.Glu629Ala	missense	Exon 13 of 16	NP_001123645.1	P10242-4
	MYB	NM_001161656.2		c.1877A>C	p.Glu626Ala	missense	Exon 13 of 16	NP_001155128.1	P10242-7
	MYB	NM_001161658.2		c.1838A>C	p.Glu613Ala	missense	Exon 13 of 16	NP_001155130.1	P10242-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYB	ENST00000341911.10	TSL:1 MANE Select	c.1886A>C	p.Glu629Ala	missense	Exon 13 of 16	ENSP00000339992.5	P10242-4
	MYB	ENST00000528774.5	TSL:1	c.1877A>C	p.Glu626Ala	missense	Exon 13 of 16	ENSP00000434723.1	P10242-7
	MYB	ENST00000534121.5	TSL:1	c.1838A>C	p.Glu613Ala	missense	Exon 13 of 16	ENSP00000432851.1	P10242-8

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152182 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000506 AC: 127 AN: 250926 AF XY: 0.000324

Gnomad AFR exome AF: 0.00708

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000179 AC: 262 AN: 1461840 Hom.: 2 Cov.: 31 AF XY: 0.000138 AC XY: 100 AN XY: 727212

African (AFR) AF: 0.00612 AC: 205 AN: 33480

American (AMR) AF: 0.000335 AC: 15 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111984

Other (OTH) AF: 0.000397 AC: 24 AN: 60396

GnomAD4 genome AF: 0.00192 AC: 293 AN: 152300 Hom.: 1 Cov.: 32 AF XY: 0.00189 AC XY: 141 AN XY: 74468

African (AFR) AF: 0.00657 AC: 273 AN: 41562

American (AMR) AF: 0.000784 AC: 12 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.000736 Hom.: 2

Bravo AF: 0.00229

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MYB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L
PhyloP100		8.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.14
Sift	Benign	0.033	D
Sift4G	Benign	0.43	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.48
Mutation Taster		=81/19	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs73555746;

hg19: chr6-135521489;

COSMIC: COSV104413622;