12-77024180-T-G

Variant names:

• chr12-77024180-T-G
• rs141743480
• NM_203394.3:c.2571A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_203394.3(E2F7):​c.2571A>C​(p.Pro857Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,610,532 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: E2F7 NM_203394.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0240

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009202778).
• BP6: Variant 12-77024180-T-G is Benign according to our data. Variant chr12-77024180-T-G is described in ClinVar as [Benign]. Clinvar id is 707899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.024 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F7	NM_203394.3	c.2571A>C	p.Pro857Pro	synonymous_variant	Exon 13 of 13	ENST00000322886.12	NP_976328.2
E2F7	XM_011537966.3	c.2436A>C	p.Pro812Pro	synonymous_variant	Exon 12 of 12		XP_011536268.1
E2F7	XM_011537969.3	c.2268A>C	p.Pro756Pro	synonymous_variant	Exon 12 of 12		XP_011536271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F7	ENST00000322886.12	c.2571A>C	p.Pro857Pro	synonymous_variant	Exon 13 of 13	1	NM_203394.3	ENSP00000323246.7
E2F7	ENST00000416496.6	c.2146A>C	p.Ser716Arg	missense_variant	Exon 12 of 12	5		ENSP00000393639.2

Frequencies

GnomAD3 genomes AF: 0.00100 AC: 152 AN: 151980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000272 AC: 67 AN: 246056 AF XY: 0.000248

Gnomad AFR exome AF: 0.00341

Gnomad AMR exome AF: 0.000241

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000336

GnomAD4 exome AF: 0.000117 AC: 171 AN: 1458434 Hom.: 1 Cov.: 31 AF XY: 0.0000923 AC XY: 67 AN XY: 725632

Gnomad4 AFR exome AF: 0.00393 AC: 130 AN: 33060

Gnomad4 AMR exome AF: 0.000321 AC: 14 AN: 43558

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25966

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39682

Gnomad4 SAS exome AF: 0.0000700 AC: 6 AN: 85660

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53388

Gnomad4 NFE exome AF: 9.00e-7 AC: 1 AN: 1111196

Gnomad4 Remaining exome AF: 0.000332 AC: 20 AN: 60186

GnomAD4 genome AF: 0.00101 AC: 153 AN: 152098 Hom.: 0 Cov.: 32 AF XY: 0.000874 AC XY: 65 AN XY: 74356

Gnomad4 AFR AF: 0.00330 AC: 0.00330009 AN: 0.00330009

Gnomad4 AMR AF: 0.000786 AC: 0.000785855 AN: 0.000785855

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000208 AC: 0.000208333 AN: 0.000208333

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.00142 AC: 0.00142045 AN: 0.00142045

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.00131

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000247 AC: 30

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.1
DANN	Uncertain	1.0
Eigen	Benign	0.059
Eigen_PC	Benign	-0.0035
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0092	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Polyphen		0.96	D
Vest4		0.23
MutPred		0.24		Gain of catalytic residue at S716 (P = 0.001);
MVP		0.39
ClinPred		0.030	T
GERP RS		2.1
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs141743480; hg19: chr12-77417960;