Variant 8-66566083-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080416.4(MYBL1):c.2111A>G(p.Lys704Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,530,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

MYBL1
NM_001080416.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

MYBL1 (HGNC:7547): (MYB proto-oncogene like 1) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYBL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07071084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBL1	NM_001080416.4 linkuse as main transcript	c.2111A>G	p.Lys704Arg	missense_variant	15/16	ENST00000522677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBL1	ENST00000522677.8 linkuse as main transcript	c.2111A>G	p.Lys704Arg	missense_variant	15/16	1	NM_001080416.4	A1	P10243-1
MYBL1	ENST00000524176.2 linkuse as main transcript	c.1950+601A>G		intron_variant		1		P4	P10243-2
MYBL1	ENST00000517885.5 linkuse as main transcript	c.1085A>G	p.Lys362Arg	missense_variant	11/12	5
MYBL1	ENST00000522419.1 linkuse as main transcript	n.189-576A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000700

AC:

AN:

142778

Hom.:

AF XY:

0.00

AC XY:

AN XY:

75274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000506

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000290

AC:

AN:

1378270

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

AN XY:

679718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000317

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000283

Gnomad4 SAS exome

AF:

0.0000134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.35e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.2111A>G (p.K704R) alteration is located in exon 15 (coding exon 15) of the MYBL1 gene. This alteration results from a A to G substitution at nucleotide position 2111, causing the lysine (K) at amino acid position 704 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.098

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;.

MutationTaster

Benign

0.91

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.043

Sift

Benign

0.28

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.0010

B;.

Vest4

0.088

MutPred

0.29

Loss of methylation at K704 (P = 0.0097);.;

MVP

0.068

MPC

0.078

ClinPred

0.085

GERP RS

4.6

Varity_R

0.068

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over