rs137938238

Variant names:

• chr11-19224728-T-C
• rs137938238
• NM_024680.4:c.2534A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-19224728-T-C
• chr11-19224728-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024680.4(E2F8):​c.2534A>G​(p.Asn845Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,614,212 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (13 hom.)
• Consequence: E2F8 NM_024680.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.338
• Publications: 2 publications found

Genes affected

E2F8 (HGNC:24727): (E2F transcription factor 8) This gene encodes a member of a family of transcription factors which regulate the expression of genes required for progression through the cell cycle. The encoded protein regulates progression from G1 to S phase by ensuring the nucleus divides at the proper time. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2012]

CSRP3-AS1 (HGNC:54183): (CSRP3 and E2F8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016845167).
• BP6: Variant 11-19224728-T-C is Benign according to our data. Variant chr11-19224728-T-C is described in ClinVar as Benign. ClinVar VariationId is 790408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00651 (991/152318) while in subpopulation AFR AF = 0.0227 (943/41566). AF 95% confidence interval is 0.0215. There are 12 homozygotes in GnomAd4. There are 442 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024680.4. 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
	E2F8	NM_024680.4	MANE Select	c.2534A>G	p.Asn845Ser	missense	Exon 13 of 13	NP_078956.2
	E2F8	NM_001256371.2		c.2534A>G	p.Asn845Ser	missense	Exon 13 of 13	NP_001243300.1	A0AVK6
	E2F8	NM_001256372.1		c.2534A>G	p.Asn845Ser	missense	Exon 13 of 13	NP_001243301.1	A0AVK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F8	ENST00000250024.9	TSL:1 MANE Select	c.2534A>G	p.Asn845Ser	missense	Exon 13 of 13	ENSP00000250024.4	A0AVK6
	E2F8	ENST00000928104.1		c.2558A>G	p.Asn853Ser	missense	Exon 13 of 13	ENSP00000598163.1
	E2F8	ENST00000527884.5	TSL:2	c.2534A>G	p.Asn845Ser	missense	Exon 13 of 13	ENSP00000434199.1	A0AVK6

Frequencies

GnomAD3 genomes AF: 0.00651 AC: 991 AN: 152200 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00163 AC: 409 AN: 251474 AF XY: 0.00127

Gnomad AFR exome AF: 0.0221

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000647 AC: 946 AN: 1461894 Hom.: 13 Cov.: 31 AF XY: 0.000568 AC XY: 413 AN XY: 727248

African (AFR) AF: 0.0231 AC: 775 AN: 33480

American (AMR) AF: 0.00103 AC: 46 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1112012

Other (OTH) AF: 0.00154 AC: 93 AN: 60396

GnomAD4 genome AF: 0.00651 AC: 991 AN: 152318 Hom.: 12 Cov.: 32 AF XY: 0.00593 AC XY: 442 AN XY: 74488

African (AFR) AF: 0.0227 AC: 943 AN: 41566

American (AMR) AF: 0.00222 AC: 34 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68020

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00240 Hom.: 5

Bravo AF: 0.00752

ESP6500AA AF: 0.0191 AC: 84

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00201 AC: 244

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.95
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.34
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.047
Sift	Benign	0.18	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.044
MVP		0.11
MPC		0.11
ClinPred		0.0056	T
GERP RS		-1.6
Varity_R		0.033
gMVP		0.15
Mutation Taster		=100/0	polymorphism

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: rs137938238; hg19: chr11-19246275; COSMIC: COSV106084605; COSMIC: COSV106084605;