NM_001949.5:c.394-37723C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001949.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F3	NM_001949.5	MANE Select	c.394-37723C>T		intron	N/A	NP_001940.1
	E2F3	NM_001243076.3		c.19-37723C>T		intron	N/A	NP_001230005.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F3	ENST00000346618.8	TSL:1 MANE Select	c.394-37723C>T		intron	N/A	ENSP00000262904.4
	E2F3	ENST00000535432.2	TSL:1	c.19-37723C>T		intron	N/A	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

African (AFR) AF: 0.298 AC: 12290 AN: 41300

American (AMR) AF: 0.637 AC: 9716 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2019 AN: 3462

East Asian (EAS) AF: 0.703 AC: 3623 AN: 5152

South Asian (SAS) AF: 0.568 AC: 2729 AN: 4804

European-Finnish (FIN) AF: 0.647 AC: 6813 AN: 10536

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 45979 AN: 67928

Other (OTH) AF: 0.579 AC: 1222 AN: 2110

Alfa AF: 0.635 Hom.: 52513

Bravo AF: 0.550

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.33
DANN	Benign	0.35
PhyloP100		-1.0
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: rs7760528; hg19: chr6-20442354;