rs12660713

Positions:

• chr6-135196858-G-A

Variant summary

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

The NM_001130173.2(MYB):​c.1204-103G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,584,834 control chromosomes in the GnomAD database, including 9,927 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 0.10 (853 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9074 hom.)
• Consequence: MYB NM_001130173.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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]

LOC105378011 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYB	NM_001130173.2	c.1204-103G>A		intron_variant		ENST00000341911.10	NP_001123645.1
LOC105378011	XR_001744368.2	n.279-858C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYB	ENST00000341911.10	c.1204-103G>A		intron_variant		1	NM_001130173.2	ENSP00000339992	A1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15551 AN: 152052 Hom.: 855 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0964

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0938

GnomAD4 exome AF: 0.111 AC: 159031 AN: 1432664 Hom.: 9074 Cov.: 31 AF XY: 0.112 AC XY: 79378 AN XY: 711452

Gnomad4 AFR exome AF: 0.0893

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0897

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0886

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.102 AC: 15553 AN: 152170 Hom.: 853 Cov.: 32 AF XY: 0.101 AC XY: 7484 AN XY: 74382

Gnomad4 AFR AF: 0.0889

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.0966

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0867

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0928

Alfa AF: 0.110 Hom.: 196

Bravo AF: 0.101

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.68

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: rs12660713; hg19: chr6-135517996; COSMIC: COSV57196915; COSMIC: COSV57196915;