chr6-135182647-C-T

Variant names:

• chr6-135182647-C-T
• rs210962
• NM_001130173.2:c.23+1111C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.23+1111C>T		intron	N/A	NP_001123645.1	P10242-4
	MYB	NM_001161656.2		c.23+1111C>T		intron	N/A	NP_001155128.1	P10242-7
	MYB	NM_001161658.2		c.23+1111C>T		intron	N/A	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.23+1111C>T		intron	N/A	ENSP00000339992.5	P10242-4
	MYB	ENST00000528774.5	TSL:1	c.23+1111C>T		intron	N/A	ENSP00000434723.1	P10242-7
	MYB	ENST00000534121.5	TSL:1	c.23+1111C>T		intron	N/A	ENSP00000432851.1	P10242-8

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

African (AFR) AF: 0.475 AC: 19713 AN: 41502

American (AMR) AF: 0.307 AC: 4699 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1921 AN: 5162

South Asian (SAS) AF: 0.349 AC: 1681 AN: 4820

European-Finnish (FIN) AF: 0.294 AC: 3114 AN: 10598

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15651 AN: 68002

Other (OTH) AF: 0.329 AC: 696 AN: 2116

Alfa AF: 0.270 Hom.: 964

Bravo AF: 0.329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.6
DANN	Benign	0.93
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs210962; hg19: chr6-135503785;