chr12-77025593-C-T

Variant names:

• chr12-77025593-C-T
• rs138091106
• NM_203394.3:c.2530G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_203394.3(E2F7):​c.2530G>A​(p.Val844Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V844L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: E2F7 NM_203394.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.18
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047090054).
• BP6: Variant 12-77025593-C-T is Benign according to our data. Variant chr12-77025593-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3086765.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2530G>A	p.Val844Met	missense	Exon 12 of 13	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.2530G>A	p.Val844Met	missense	Exon 12 of 13	ENSP00000323246.7	Q96AV8-1
	E2F7	ENST00000919447.1		c.2491G>A	p.Val831Met	missense	Exon 12 of 13	ENSP00000589506.1
	E2F7	ENST00000919446.1		c.2395G>A	p.Val799Met	missense	Exon 11 of 12	ENSP00000589505.1

Frequencies

GnomAD3 genomes AF: 0.000539 AC: 82 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000199 AC: 50 AN: 251406 AF XY: 0.000147

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000121 AC: 177 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.000106 AC XY: 77 AN XY: 727248

African (AFR) AF: 0.00197 AC: 66 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000818 AC: 91 AN: 1112010

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.000538 AC: 82 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000483 AC XY: 36 AN XY: 74466

African (AFR) AF: 0.00178 AC: 74 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.000582

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000255 AC: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.82
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-3.2
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.0090
Sift	Benign	0.35	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.053
MVP		0.28
MPC		0.30
ClinPred		0.0083	T
GERP RS		-7.7
Varity_R		0.026
gMVP		0.17
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs138091106; hg19: chr12-77419373; COSMIC: COSV59738898; COSMIC: COSV59738898;