rs3730391

Variant names:

• chr16-67192147-C-A
• rs3730391
• NM_001950.4:c.-81C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-67192147-C-A
• chr16-67192147-C-G
• chr16-67192147-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001950.4(E2F4):​c.-81C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,181,230 control chromosomes in the GnomAD database, including 22 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 0.0034 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (21 hom.)
• Consequence: E2F4 NM_001950.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

Genes affected

E2F4 (HGNC:3118): (E2F transcription factor 4) 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 binds to all three of the tumor suppressor proteins pRB, p107 and p130, but with higher affinity to the last two. It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High AC in GnomAd4 at 523 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4	c.-81C>A		upstream_gene_variant		ENST00000379378.8	NP_001941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F4	ENST00000379378.8	c.-81C>A		upstream_gene_variant		1	NM_001950.4	ENSP00000368686.3

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 524 AN: 152176 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00467

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00471 AC: 4847 AN: 1028936 Hom.: 21 Cov.: 24 AF XY: 0.00482 AC XY: 2340 AN XY: 485090

Gnomad4 AFR exome AF: 0.000428

Gnomad4 AMR exome AF: 0.00409

Gnomad4 ASJ exome AF: 0.0282

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00483

Gnomad4 FIN exome AF: 0.000645

Gnomad4 NFE exome AF: 0.00463

Gnomad4 OTH exome AF: 0.00603

GnomAD4 genome AF: 0.00343 AC: 523 AN: 152294 Hom.: 1 Cov.: 33 AF XY: 0.00318 AC XY: 237 AN XY: 74478

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00468

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00112 Hom.: 0

Bravo AF: 0.00377

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3730391; hg19: chr16-67226050;