rs112653372

chr6-135201679-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001130173.2(MYB):c.1991C>T(p.Ser664Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,601,446 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: MYB NM_001130173.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20365056).
• BS2: High AC in GnomAd at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYB	NM_001130173.2	c.1991C>T	p.Ser664Leu	missense_variant	14/16	ENST00000341911.10
LOC105378011	XR_001744368.2	n.279-5679G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYB	ENST00000341911.10	c.1991C>T	p.Ser664Leu	missense_variant	14/16	1	NM_001130173.2	A1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000327 AC: 8 AN: 244718 Hom.: 0 AF XY: 0.0000226 AC XY: 3 AN XY: 132578

Gnomad AFR exome AF: 0.000448

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000564

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1449252 Hom.: 0 Cov.: 30 AF XY: 0.00000833 AC XY: 6 AN XY: 720340

Gnomad4 AFR exome AF: 0.000396

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152194 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74350

Gnomad4 AFR AF: 0.000531

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000275 Hom.: 0

Bravo AF: 0.000181

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	-0.020
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T;T;.;T;T;.;.;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T;T;T
Polyphen		1.0	D;D;.;.;D;D;.;.;.;.;.
Vest4		0.51
MVP		0.75
MPC		0.24
ClinPred		0.097	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.079
gMVP		0.19

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: rs112653372; hg19: chr6-135522817; COSMIC: COSV104607974; COSMIC: COSV104607974;