8-66592542-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PP3_Moderate BP6_Moderate BS1 BS2

The NM_001080416.4(MYBL1):c.765A>G(p.Gln255=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000851 in 1,566,410 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (2 hom.)
• Consequence: MYBL1 NM_001080416.4 splice_region, synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.205

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 -8 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 8-66592542-T-C is Benign according to our data. Variant chr8-66592542-T-C is described in ClinVar as [Benign]. Clinvar id is 791292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00482 (733/152086) while in subpopulation AFR AF= 0.0171 (709/41486). AF 95% confidence interval is 0.016. There are 12 homozygotes in gnomad4. There are 340 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 726 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBL1	NM_001080416.4	c.765A>G	p.Gln255=	splice_region_variant, synonymous_variant	8/16	ENST00000522677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBL1	ENST00000522677.8	c.765A>G	p.Gln255=	splice_region_variant, synonymous_variant	8/16	1	NM_001080416.4	A1
MYBL1	ENST00000524176.2	c.765A>G	p.Gln255=	splice_region_variant, synonymous_variant	8/15	1		P4
MYBL1	ENST00000517885.5	c.317+4983A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00478 AC: 726 AN: 151968 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

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: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00121 AC: 271 AN: 223362 Hom.: 3 AF XY: 0.000867 AC XY: 106 AN XY: 122218

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.000777

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000375

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000187

Gnomad OTH exome AF: 0.000541

GnomAD4 exome AF: 0.000424 AC: 600 AN: 1414324 Hom.: 2 Cov.: 24 AF XY: 0.000360 AC XY: 254 AN XY: 705020

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.000798

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000369

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000129

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00482 AC: 733 AN: 152086 Hom.: 12 Cov.: 32 AF XY: 0.00457 AC XY: 340 AN XY: 74366

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00128 Hom.: 0

Bravo AF: 0.00537

Asia WGS AF: 0.00174 AC: 6 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	20
Dann	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.92		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.92		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs148388060; hg19: chr8-67504777; COSMIC: COSV104440190; COSMIC: COSV104440190;