6-20442123-C-T

Variant names:

• chr6-20442123-C-T
• rs7760528
• NM_001949.5:c.394-37723C>T

Variant summary

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

The NM_001949.5(E2F3):​c.394-37723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,734 control chromosomes in the GnomAD database, including 25,936 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 0.56 (25936 hom., cov: 30)
• Consequence: E2F3 NM_001949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

E2F3 (HGNC:3115): (E2F transcription factor 3) This gene encodes a member of a small family of transcription factors that function through binding of DP interaction partner proteins. The encoded protein recognizes a specific sequence motif in DNA and interacts directly with the retinoblastoma protein (pRB) to regulate the expression of genes involved in the cell cycle. Altered copy number and activity of this gene have been observed in a number of human cancers. There are pseudogenes for this gene on chromosomes 2 and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F3	NM_001949.5	c.394-37723C>T		intron_variant	Intron 1 of 6	ENST00000346618.8	NP_001940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F3	ENST00000346618.8	c.394-37723C>T		intron_variant	Intron 1 of 6	1	NM_001949.5	ENSP00000262904.4
E2F3	ENST00000535432.2	c.19-37723C>T		intron_variant	Intron 1 of 6	1		ENSP00000443418.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85133 AN: 151616 Hom.: 25932 Cov.: 30

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.561 AC: 85144 AN: 151734 Hom.: 25936 Cov.: 30 AF XY: 0.563 AC XY: 41736 AN XY: 74176

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.579

Alfa AF: 0.645 Hom.: 42455

Bravo AF: 0.550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.33
DANN	Benign	0.35

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: rs7760528; hg19: chr6-20442354;