20-2707972-A-G

Position:

• chr20-2707972-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395167.1(EBF4):​c.440A>G​(p.Lys147Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EBF4 NM_001395167.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.22

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF4	NM_001395167.1	c.440A>G	p.Lys147Arg	missense_variant	5/17	ENST00000609451.6	NP_001382096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF4	ENST00000609451.6	c.440A>G	p.Lys147Arg	missense_variant	5/17	5	NM_001395167.1	ENSP00000477023	P1
EBF4	ENST00000380648.9	c.428A>G	p.Lys143Arg	missense_variant	6/18	5		ENSP00000370022
EBF4	ENST00000469215.2	c.212A>G	p.Lys71Arg	missense_variant	4/6	5		ENSP00000501409
EBF4	ENST00000449079.7	c.428A>G	p.Lys143Arg	missense_variant, NMD_transcript_variant	6/18	2		ENSP00000405003

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

May 27, 2022

The c.428A>G (p.K143R) alteration is located in exon 6 (coding exon 6) of the EBF4 gene. This alteration results from a A to G substitution at nucleotide position 428, causing the lysine (K) at amino acid position 143 to be replaced by an arginine (R). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.5	.;.;M;.
MutationTaster	Benign	0.95	D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.5	N;.;.;.
REVEL	Benign	0.26
Sift	Benign	0.053	T;.;.;.
Sift4G	Benign	0.082	T;T;T;T
Polyphen		0.089	B;.;.;.
Vest4		0.76
MutPred		0.24		Loss of methylation at K143 (P = 0.0032);.;.;.;
MVP		0.74
MPC		0.50
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.17
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr20-2688618;