rs3213182

Variant names:

• chr20-33675427-A-C
• rs3213182
• NM_005225.3:c.*1305T>G

Variant summary

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

The NM_005225.3(E2F1):​c.*1305T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 162,480 control chromosomes in the GnomAD database, including 608 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 0.072 (570 hom., cov: 32)
  • Exomes 𝑓: 0.078 (38 hom.)
• Consequence: E2F1 NM_005225.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

Genes affected

E2F1 (HGNC:3113): (E2F transcription factor 1) The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis. [provided by RefSeq, Jul 2008]

NECAB3 (HGNC:15851): (N-terminal EF-hand calcium binding protein 3) The protein encoded by this gene interacts with the amino-terminal domain of the neuron-specific X11-like protein (X11L), inhibits the association of X11L with amyloid precursor protein through a non-competitive mechanism, and abolishes the suppression of beta-amyloid production by X11L. This protein, together with X11L, may play an important role in the regulatory system of amyloid precursor protein metabolism and beta-amyloid generation. The protein is phosphorylated by NIMA-related expressed kinase 2, and localizes to the Golgi apparatus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000271803 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F1	NM_005225.3	c.*1305T>G		downstream_gene_variant		ENST00000343380.6	NP_005216.1
NECAB3	XM_047440369.1	c.-602T>G		upstream_gene_variant			XP_047296325.1
NECAB3	XM_047440370.1	c.-602T>G		upstream_gene_variant			XP_047296326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F1	ENST00000343380.6	c.*1305T>G		downstream_gene_variant		1	NM_005225.3	ENSP00000345571.5
ENSG00000271803	ENST00000606866.1	n.*47A>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10942 AN: 152010 Hom.: 570 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0871

GnomAD4 exome AF: 0.0782 AC: 810 AN: 10352 Hom.: 38 Cov.: 0 AF XY: 0.0805 AC XY: 440 AN XY: 5464

Gnomad4 AFR exome AF: 0.0169 AC: 4 AN: 236

Gnomad4 AMR exome AF: 0.0340 AC: 7 AN: 206

Gnomad4 ASJ exome AF: 0.156 AC: 52 AN: 334

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 1194

Gnomad4 SAS exome AF: 0.0303 AC: 2 AN: 66

Gnomad4 FIN exome AF: 0.0601 AC: 76 AN: 1264

Gnomad4 NFE exome AF: 0.0953 AC: 612 AN: 6424

Gnomad4 Remaining exome AF: 0.0927 AC: 53 AN: 572

GnomAD4 genome AF: 0.0719 AC: 10942 AN: 152128 Hom.: 570 Cov.: 32 AF XY: 0.0691 AC XY: 5137 AN XY: 74374

Gnomad4 AFR AF: 0.0183 AC: 0.0182554 AN: 0.0182554

Gnomad4 AMR AF: 0.0624 AC: 0.0623609 AN: 0.0623609

Gnomad4 ASJ AF: 0.151 AC: 0.151384 AN: 0.151384

Gnomad4 EAS AF: 0.000194 AC: 0.00019425 AN: 0.00019425

Gnomad4 SAS AF: 0.0424 AC: 0.0424255 AN: 0.0424255

Gnomad4 FIN AF: 0.0625 AC: 0.0625 AN: 0.0625

Gnomad4 NFE AF: 0.110 AC: 0.110047 AN: 0.110047

Gnomad4 OTH AF: 0.0871 AC: 0.0871429 AN: 0.0871429

Alfa AF: 0.0924 Hom.: 882

Bravo AF: 0.0712

Asia WGS AF: 0.0270 AC: 95 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	5.7
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3213182; hg19: chr20-32263233;