Genetic Variant LOC105378011:n.177-3742C>T (chr6-135219242-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XR_001744368.2(LOC105378011):n.177-3742C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 186,856 control chromosomes in the GnomAD database, including 34,391 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 30120 hom., cov: 33)

Exomes 𝑓: 0.49 ( 4271 hom. )

Consequence

LOC105378011
XR_001744368.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

Publications

7 publications found

Variant links:

COSMIC-nc: COSV57197014

Genes affected

LOC105378011 (HGNC:):

LOC105378011 links:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341911.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYB	NM_001130173.2	MANE Select	c.*1262G>A	downstream_gene	N/A	NP_001123645.1
MYB	NM_001161656.2		c.*1262G>A	downstream_gene	N/A	NP_001155128.1
MYB	NM_001161658.2		c.*1262G>A	downstream_gene	N/A	NP_001155130.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYB	ENST00000341911.10	TSL:1 MANE Select	c.*1262G>A	downstream_gene	N/A	ENSP00000339992.5
MYB	ENST00000367814.8	TSL:1	c.*1262G>A	downstream_gene	N/A	ENSP00000356788.4
MYB	ENST00000442647.7	TSL:1	c.*1262G>A	downstream_gene	N/A	ENSP00000410825.2

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91357

AN:

152016

Hom.:

30061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.377

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.520

GnomAD4 exome

AF:

0.490

AC:

17011

AN:

34722

Hom.:

4271

AF XY:

0.491

AC XY:

7889

AN XY:

16054

show subpopulations

African (AFR)

AF:

0.871

AC:

1089

AN:

1250

American (AMR)

AF:

0.425

AC:

360

AN:

848

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

833

AN:

2234

East Asian (EAS)

AF:

0.451

AC:

2925

AN:

6480

South Asian (SAS)

AF:

0.546

AC:

154

AN:

282

European-Finnish (FIN)

AF:

0.593

AC:

262

AN:

442

Middle Eastern (MID)

AF:

0.421

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.492

AC:

9926

AN:

20160

Other (OTH)

AF:

0.488

AC:

1372

AN:

2812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

420

840

1259

1679

2099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.601

AC:

91481

AN:

152134

Hom.:

30120

Cov.:

AF XY:

0.600

AC XY:

44622

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.882

AC:

36650

AN:

41536

American (AMR)

AF:

0.437

AC:

6676

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

1308

AN:

3470

East Asian (EAS)

AF:

0.503

AC:

2605

AN:

5180

South Asian (SAS)

AF:

0.506

AC:

2441

AN:

4824

European-Finnish (FIN)

AF:

0.577

AC:

6083

AN:

10538

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34236

AN:

67992

Other (OTH)

AF:

0.526

AC:

1111

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1670

3340

5009

6679

8349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.528

Hom.:

65809

Bravo

AF:

0.597

Asia WGS

AF:

0.549

AC:

1908

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.5

(source)

DANN

Benign

0.67

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over