6-135189970-A-T

Variant names:

• chr6-135189970-A-T
• rs210796
• NM_001130173.2:c.306+87A>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.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
• Publications: 6 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=-0.82).
• 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 rank	MANE	Protein	UniProt
MYB	NM_001130173.2	c.306+87A>T		intron_variant	Intron 4 of 15	ENST00000341911.10	NP_001123645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYB	ENST00000341911.10	c.306+87A>T		intron_variant	Intron 4 of 15	1	NM_001130173.2	ENSP00000339992.5

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

African (AFR) AF: 0.294 AC: 8705 AN: 29646

American (AMR) AF: 0.450 AC: 16956 AN: 37682

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 8825 AN: 23476

East Asian (EAS) AF: 0.350 AC: 13543 AN: 38684

South Asian (SAS) AF: 0.403 AC: 31296 AN: 77648

European-Finnish (FIN) AF: 0.407 AC: 20957 AN: 51548

Middle Eastern (MID) AF: 0.295 AC: 1573 AN: 5328

European-Non Finnish (NFE) AF: 0.400 AC: 399277 AN: 998036

Other (OTH) AF: 0.395 AC: 21743 AN: 55084

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

African (AFR) AF: 0.304 AC: 12630 AN: 41482

American (AMR) AF: 0.405 AC: 6197 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2079 AN: 5186

South Asian (SAS) AF: 0.382 AC: 1843 AN: 4826

European-Finnish (FIN) AF: 0.417 AC: 4402 AN: 10552

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26431 AN: 67972

Other (OTH) AF: 0.374 AC: 791 AN: 2114

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
PhyloP100		-0.71
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: rs210796; hg19: chr6-135511108; COSMIC: COSV57200807;