6-20414822-A-G

Variant names:

• chr6-20414822-A-G
• rs911361
• NM_001949.5:c.393+12197A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001949.5(E2F3):​c.393+12197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,974 control chromosomes in the GnomAD database, including 30,640 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 0.63 (30640 hom., cov: 31)
• Consequence: E2F3 NM_001949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F3	NM_001949.5	c.393+12197A>G		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.393+12197A>G		intron_variant	Intron 1 of 6	1	NM_001949.5	ENSP00000262904.4
E2F3	ENST00000535432.2	c.18+10990A>G		intron_variant	Intron 1 of 6	1		ENSP00000443418.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95681 AN: 151856 Hom.: 30604 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.630 AC: 95767 AN: 151974 Hom.: 30640 Cov.: 31 AF XY: 0.629 AC XY: 46732 AN XY: 74266

African (AFR) AF: 0.750 AC: 31098 AN: 41456

American (AMR) AF: 0.637 AC: 9728 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2156 AN: 3470

East Asian (EAS) AF: 0.660 AC: 3410 AN: 5166

South Asian (SAS) AF: 0.653 AC: 3143 AN: 4816

European-Finnish (FIN) AF: 0.527 AC: 5557 AN: 10540

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38684 AN: 67930

Other (OTH) AF: 0.622 AC: 1313 AN: 2110

Alfa AF: 0.589 Hom.: 45107

Bravo AF: 0.643

Asia WGS AF: 0.663 AC: 2306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.45
PhyloP100		0.25
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: rs911361; hg19: chr6-20415053;