6-135189970-A-T

Position:

• chr6-135189970-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130173.2(MYB):​c.306+87A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,469,238 control chromosomes in the GnomAD database, including 114,635 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 0.37 (10489 hom., cov: 33)
  • Exomes 𝑓: 0.40 (104146 hom.)
• Consequence: MYB NM_001130173.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYB	NM_001130173.2	c.306+87A>T		intron_variant		ENST00000341911.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYB	ENST00000341911.10	c.306+87A>T		intron_variant		1	NM_001130173.2	A1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56017 AN: 151988 Hom.: 10485 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.397 AC: 522875 AN: 1317132 Hom.: 104146 Cov.: 18 AF XY: 0.396 AC XY: 260664 AN XY: 657878

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.368 AC: 56039 AN: 152106 Hom.: 10489 Cov.: 33 AF XY: 0.371 AC XY: 27565 AN XY: 74354

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.374

Alfa AF: 0.382 Hom.: 1405

Bravo AF: 0.365

Asia WGS AF: 0.410 AC: 1423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.62

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: rs210796; hg19: chr6-135511108; COSMIC: COSV57200807;