chr6-135189777-CTTTA-C

Position:

• chr6-135189777-CTTTA-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001130173.2(MYB):​c.214-10_214-7del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00083 in 1,610,042 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (3 hom.)
• Consequence: MYB NM_001130173.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.74

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-135189777-CTTTA-C is Benign according to our data. Variant chr6-135189777-CTTTA-C is described in ClinVar as [Benign]. Clinvar id is 716353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 661 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYB	NM_001130173.2	c.214-10_214-7del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000341911.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYB	ENST00000341911.10	c.214-10_214-7del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001130173.2	A1

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 658 AN: 152180 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

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: 0.0000735

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00116 AC: 289 AN: 250150 Hom.: 5 AF XY: 0.000791 AC XY: 107 AN XY: 135212

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.000731

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000463 AC: 675 AN: 1457744 Hom.: 3 AF XY: 0.000419 AC XY: 304 AN XY: 725462

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.000743

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000815

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000451

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.00434 AC: 661 AN: 152298 Hom.: 5 Cov.: 32 AF XY: 0.00396 AC XY: 295 AN XY: 74470

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00230 Hom.: 1

Bravo AF: 0.00508

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs112749262; hg19: chr6-135510915;