rs12660713

Variant names:

• chr6-135196858-G-A
• rs12660713
• NM_001130173.2:c.1204-103G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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]

LOC105378011 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.1204-103G>A		intron	N/A	NP_001123645.1	P10242-4
	MYB	NM_001161656.2		c.1195-103G>A		intron	N/A	NP_001155128.1	P10242-7
	MYB	NM_001161658.2		c.1156-103G>A		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.1204-103G>A		intron	N/A	ENSP00000339992.5	P10242-4
	MYB	ENST00000528774.5	TSL:1	c.1195-103G>A		intron	N/A	ENSP00000434723.1	P10242-7
	MYB	ENST00000534121.5	TSL:1	c.1156-103G>A		intron	N/A	ENSP00000432851.1	P10242-8

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

African (AFR) AF: 0.0893 AC: 2932 AN: 32830

American (AMR) AF: 0.100 AC: 4287 AN: 42764

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 2279 AN: 25412

East Asian (EAS) AF: 0.123 AC: 4861 AN: 39428

South Asian (SAS) AF: 0.134 AC: 11266 AN: 84036

European-Finnish (FIN) AF: 0.0886 AC: 3562 AN: 40210

Middle Eastern (MID) AF: 0.0793 AC: 448 AN: 5646

European-Non Finnish (NFE) AF: 0.112 AC: 123015 AN: 1102850

Other (OTH) AF: 0.107 AC: 6381 AN: 59488

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

African (AFR) AF: 0.0889 AC: 3690 AN: 41528

American (AMR) AF: 0.104 AC: 1588 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.0966 AC: 500 AN: 5174

South Asian (SAS) AF: 0.139 AC: 672 AN: 4822

European-Finnish (FIN) AF: 0.0867 AC: 918 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7605 AN: 67978

Other (OTH) AF: 0.0928 AC: 196 AN: 2112

Alfa AF: 0.109 Hom.: 323

Bravo AF: 0.101

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		-0.30
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: rs12660713; hg19: chr6-135517996; COSMIC: COSV57196915; COSMIC: COSV57196915;