chr6-135193420-T-G

Variant names:

• chr6-135193420-T-G
• rs210798
• NM_001130173.2:c.763-418T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130173.2(MYB):​c.763-418T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,006 control chromosomes in the GnomAD database, including 27,264 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 0.59 (27264 hom., cov: 33)
• Consequence: MYB NM_001130173.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYB	NM_001130173.2	c.763-418T>G		intron_variant	Intron 6 of 15	ENST00000341911.10	NP_001123645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYB	ENST00000341911.10	c.763-418T>G		intron_variant	Intron 6 of 15	1	NM_001130173.2	ENSP00000339992.5

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89212 AN: 151888 Hom.: 27232 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.588 AC: 89304 AN: 152006 Hom.: 27264 Cov.: 33 AF XY: 0.585 AC XY: 43442 AN XY: 74312

African (AFR) AF: 0.780 AC: 32357 AN: 41498

American (AMR) AF: 0.553 AC: 8457 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2581 AN: 5170

South Asian (SAS) AF: 0.554 AC: 2668 AN: 4820

European-Finnish (FIN) AF: 0.505 AC: 5292 AN: 10486

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34635 AN: 67960

Other (OTH) AF: 0.576 AC: 1218 AN: 2114

Alfa AF: 0.555 Hom.: 7008

Bravo AF: 0.599

Asia WGS AF: 0.575 AC: 1974 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.88
PhyloP100		-0.91
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: rs210798; hg19: chr6-135514558;