20-2706020-G-T

Position:

• chr20-2706020-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395167.1(EBF4):​c.341G>T​(p.Arg114Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: EBF4 NM_001395167.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.50

Genes affected

EBF4 (HGNC:29278): (EBF family member 4) EBF4 belongs to the conserved Olf/EBF family of helix-loop-helix transcription factors, members of which play important roles in neural development and B-cell maturation (Wang et al., 2002 [PubMed 12139918]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34562492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF4	NM_001395167.1	c.341G>T	p.Arg114Leu	missense_variant	3/17	ENST00000609451.6	NP_001382096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF4	ENST00000609451.6	c.341G>T	p.Arg114Leu	missense_variant	3/17	5	NM_001395167.1	ENSP00000477023	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399326 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 690174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jan 31, 2024

The c.329G>T (p.R110L) alteration is located in exon 4 (coding exon 4) of the EBF4 gene. This alteration results from a G to T substitution at nucleotide position 329, causing the arginine (R) at amino acid position 110 to be replaced by a leucine (L). 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	0.25
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T;T
Eigen	Benign	0.044
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	.;.;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.0	D;.;.
REVEL	Benign	0.15
Sift	Benign	0.13	T;.;.
Sift4G	Benign	0.080	T;T;T
Polyphen		0.15	B;.;.
Vest4		0.40
MutPred		0.54		Loss of MoRF binding (P = 0.0081);.;.;
MVP		0.64
MPC		0.85
ClinPred		0.88	D
GERP RS		3.7
Varity_R		0.16
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-2686666;