rs10504398

Variant names:

• chr8-66574680-T-C
• rs10504398
• NM_001080416.4:c.1471-1174A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080416.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBL1	NM_001080416.4	MANE Select	c.1471-1174A>G		intron	N/A	NP_001073885.1	P10243-1
	MYBL1	NM_001144755.3		c.1471-1174A>G		intron	N/A	NP_001138227.1	P10243-2
	MYBL1	NM_001294282.2		c.1468-1174A>G		intron	N/A	NP_001281211.1	Q495G0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBL1	ENST00000522677.8	TSL:1 MANE Select	c.1471-1174A>G		intron	N/A	ENSP00000429633.2	P10243-1
	MYBL1	ENST00000524176.2	TSL:1	c.1471-1174A>G		intron	N/A	ENSP00000428011.2	P10243-2
	MYBL1	ENST00000917736.1		c.1336-1174A>G		intron	N/A	ENSP00000587795.1

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

African (AFR) AF: 0.0236 AC: 982 AN: 41580

American (AMR) AF: 0.110 AC: 1685 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1115 AN: 5186

South Asian (SAS) AF: 0.196 AC: 949 AN: 4830

European-Finnish (FIN) AF: 0.138 AC: 1471 AN: 10624

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9159 AN: 68032

Other (OTH) AF: 0.102 AC: 214 AN: 2106

Alfa AF: 0.115 Hom.: 2531

Bravo AF: 0.0952

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10504398; hg19: chr8-67486915;