rs210962

chr6-135182647-C-T

Variant summary

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

The NM_001130173.2(MYB):c.23+1111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,162 control chromosomes in the GnomAD database, including 8,632 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 0.32 (8632 hom., cov: 33)
• Consequence: MYB NM_001130173.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYB	NM_001130173.2	c.23+1111C>T		intron_variant		ENST00000341911.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYB	ENST00000341911.10	c.23+1111C>T		intron_variant		1	NM_001130173.2	A1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48393 AN: 152044 Hom.: 8621 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.318 AC: 48454 AN: 152162 Hom.: 8632 Cov.: 33 AF XY: 0.321 AC XY: 23876 AN XY: 74406

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.329

Alfa AF: 0.270 Hom.: 964

Bravo AF: 0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	9.6
Dann	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs210962; hg19: chr6-135503785;