rs10504398

chr8-66574680-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080416.4(MYBL1):c.1471-1174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,332 control chromosomes in the GnomAD database, including 1,154 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 0.11 (1154 hom., cov: 32)
• Consequence: MYBL1 NM_001080416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBL1	NM_001080416.4	c.1471-1174A>G		intron_variant		ENST00000522677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBL1	ENST00000522677.8	c.1471-1174A>G		intron_variant		1	NM_001080416.4	A1
MYBL1	ENST00000524176.2	c.1471-1174A>G		intron_variant		1		P4
MYBL1	ENST00000517885.5	c.445-1174A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15987 AN: 152214 Hom.: 1153 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0988

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.105 AC: 15995 AN: 152332 Hom.: 1154 Cov.: 32 AF XY: 0.107 AC XY: 7987 AN XY: 74496

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.102

Alfa AF: 0.124 Hom.: 1831

Bravo AF: 0.0952

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.1
Dann	Benign	0.68

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: rs10504398; hg19: chr8-67486915;