chr20-2705662-A-C

Position:

• chr20-2705662-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395167.1(EBF4):​c.223A>C​(p.Met75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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: 0.728

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054176837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBF4	NM_001395167.1	c.223A>C	p.Met75Leu	missense_variant	2/17	ENST00000609451.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBF4	ENST00000609451.6	c.223A>C	p.Met75Leu	missense_variant	2/17	5	NM_001395167.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Mar 11, 2022

The c.211A>C (p.M71L) alteration is located in exon 3 (coding exon 3) of the EBF4 gene. This alteration results from a A to C substitution at nucleotide position 211, causing the methionine (M) at amino acid position 71 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	0.088
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.76
DEOGEN2	Benign	0.0038	T;T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.50	N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.86	N;.;.
REVEL	Benign	0.053
Sift	Benign	1.0	T;.;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.31
MutPred		0.26		Gain of helix (P = 0.1736);.;.;
MVP		0.33
MPC		0.57
ClinPred		0.070	T
GERP RS		3.5
Varity_R		0.076
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-2686308;