13-40933988-G-A

Variant summary

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

The NM_172373.4(ELF1):c.1297C>T(p.Pro433Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000483 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: ELF1 NM_172373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81

Genes affected

ELF1 (HGNC:3316): (E74 like ETS transcription factor 1) This gene encodes an E26 transformation-specific related transcription factor. The encoded protein is primarily expressed in lymphoid cells and acts as both an enhancer and a repressor to regulate transcription of various genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026110858).
• BS2: High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELF1	NM_172373.4	c.1297C>T	p.Pro433Ser	missense_variant	9/9	ENST00000239882.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELF1	ENST00000239882.7	c.1297C>T	p.Pro433Ser	missense_variant	9/9	1	NM_172373.4	P1
ELF1	ENST00000635415.1	c.1297C>T	p.Pro433Ser	missense_variant	9/9	5
ELF1	ENST00000625359.1	c.1225C>T	p.Pro409Ser	missense_variant	8/8	2
ELF1	ENST00000498824.4	c.*1040C>T		3_prime_UTR_variant, NMD_transcript_variant	9/9	2

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000148 AC: 37 AN: 249988 Hom.: 0 AF XY: 0.000133 AC XY: 18 AN XY: 135268

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000472 AC: 69 AN: 1461820 Hom.: 0 Cov.: 31 AF XY: 0.0000509 AC XY: 37 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.0000993

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74360

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000293 Hom.: 0

Bravo AF: 0.0000945

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.1297C>T (p.P433S) alteration is located in exon 9 (coding exon 8) of the ELF1 gene. This alteration results from a C to T substitution at nucleotide position 1297, causing the proline (P) at amino acid position 433 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	20
Dann	Benign	0.97
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	0.024
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.026	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.98	N;.;.
REVEL	Benign	0.056
Sift	Benign	0.76	T;.;.
Sift4G	Benign	0.56	T;T;.
Polyphen		0.38	B;.;.
Vest4		0.34
MutPred		0.29		Gain of catalytic residue at R434 (P = 0.0265);.;Gain of catalytic residue at R434 (P = 0.0265);
MVP		0.38
MPC		0.17
ClinPred		0.041	T
GERP RS		5.4
Varity_R		0.10
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs756235921; hg19: chr13-41508124;