NM_203394.3:c.1124-129G>C

Variant names:

• chr12-77034171-C-G
• rs1565728
• NM_203394.3:c.1124-129G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203394.3(E2F7):​c.1124-129G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000177 in 564,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: E2F7 NM_203394.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 0 publications found

Genes affected

E2F7 (HGNC:23820): (E2F transcription factor 7) Enables DNA-binding transcription factor activity; cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in several processes, including DNA damage response, signal transduction by p53 class mediator; regulation of transcription, DNA-templated; and sprouting angiogenesis. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000294230 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F7	NM_203394.3	MANE Select	c.1124-129G>C		intron	N/A	NP_976328.2	Q96AV8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F7	ENST00000322886.12	TSL:1 MANE Select	c.1124-129G>C		intron	N/A	ENSP00000323246.7	Q96AV8-1
	E2F7	ENST00000550669.5	TSL:1	c.1124-129G>C		intron	N/A	ENSP00000448245.1	F8VSE7
	E2F7	ENST00000919447.1		c.1124-168G>C		intron	N/A	ENSP00000589506.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000177 AC: 1 AN: 564672 Hom.: 0 AF XY: 0.00000352 AC XY: 1 AN XY: 284042

African (AFR) AF: 0.00 AC: 0 AN: 12866

American (AMR) AF: 0.00 AC: 0 AN: 10362

Ashkenazi Jewish (ASJ) AF: 0.0000799 AC: 1 AN: 12520

East Asian (EAS) AF: 0.00 AC: 0 AN: 26246

South Asian (SAS) AF: 0.00 AC: 0 AN: 25486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 419206

Other (OTH) AF: 0.00 AC: 0 AN: 27894

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		-0.20

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: rs1565728; hg19: chr12-77427951;