8-66595680-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001080416.4(MYBL1):c.590G>A(p.Gly197Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,583,904 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (12 hom.)
• Consequence: MYBL1 NM_001080416.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004969716).
• BP6: Variant 8-66595680-C-T is Benign according to our data. Variant chr8-66595680-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 355 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBL1	NM_001080416.4	c.590G>A	p.Gly197Glu	missense_variant	6/16	ENST00000522677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBL1	ENST00000522677.8	c.590G>A	p.Gly197Glu	missense_variant	6/16	1	NM_001080416.4	A1
MYBL1	ENST00000524176.2	c.590G>A	p.Gly197Glu	missense_variant	6/15	1		P4
MYBL1	ENST00000517885.5	c.317+1845G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 355 AN: 152098 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00443

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00220 AC: 452 AN: 205792 Hom.: 2 AF XY: 0.00207 AC XY: 228 AN XY: 110280

Gnomad AFR exome AF: 0.000560

Gnomad AMR exome AF: 0.000169

Gnomad ASJ exome AF: 0.00174

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000195

Gnomad FIN exome AF: 0.000875

Gnomad NFE exome AF: 0.00439

Gnomad OTH exome AF: 0.00227

GnomAD4 exome AF: 0.00311 AC: 4454 AN: 1431688 Hom.: 12 Cov.: 29 AF XY: 0.00310 AC XY: 2199 AN XY: 709550

Gnomad4 AFR exome AF: 0.000518

Gnomad4 AMR exome AF: 0.000123

Gnomad4 ASJ exome AF: 0.00160

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000159

Gnomad4 FIN exome AF: 0.00102

Gnomad4 NFE exome AF: 0.00381

Gnomad4 OTH exome AF: 0.00261

GnomAD4 genome AF: 0.00233 AC: 355 AN: 152216 Hom.: 1 Cov.: 32 AF XY: 0.00202 AC XY: 150 AN XY: 74428

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000944

Gnomad4 NFE AF: 0.00443

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00330 Hom.: 2

Bravo AF: 0.00221

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.00108 AC: 4

ESP6500EA AF: 0.00465 AC: 38

ExAC AF: 0.00235 AC: 283

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

MYBL1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.11
Sift	Benign	0.087	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.20	B;.
Vest4		0.32
MVP		0.068
MPC		0.51
ClinPred		0.0075	T
GERP RS		5.5
Varity_R		0.28
gMVP		0.51

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: rs201510981; hg19: chr8-67507915; COSMIC: COSV104440176; COSMIC: COSV104440176;