chr2-25091399-G-A

Position:

• chr2-25091399-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_014971.2(EFR3B):​c.82G>A​(p.Glu28Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000358 in 1,396,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: EFR3B NM_014971.2 missense, splice_region
• Scores: Splicing: ADA: 0.0008013
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15

Genes affected

EFR3B (HGNC:29155): (EFR3 homolog B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in actin cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, EFR3B
• BP4: Computational evidence support a benign effect (MetaRNN=0.16205621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFR3B	NM_014971.2	c.82G>A	p.Glu28Lys	missense_variant, splice_region_variant	2/23	ENST00000403714.8
EFR3B	NM_001319099.2	c.-24G>A		splice_region_variant, 5_prime_UTR_variant	2/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFR3B	ENST00000403714.8	c.82G>A	p.Glu28Lys	missense_variant, splice_region_variant	2/23	5	NM_014971.2	P1
EFR3B	ENST00000401432.7	c.82G>A	p.Glu28Lys	missense_variant, splice_region_variant	2/19	2
EFR3B	ENST00000402191.5	c.-24G>A		splice_region_variant, 5_prime_UTR_variant	2/23	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000661 AC: 1 AN: 151198 Hom.: 0 AF XY: 0.0000124 AC XY: 1 AN XY: 80404

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000170

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1396882 Hom.: 0 Cov.: 32 AF XY: 0.00000581 AC XY: 4 AN XY: 689048

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: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000371

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	0.0081	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.3	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.15
Sift	Benign	0.54	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.17	B;D
Vest4		0.33
MutPred		0.41		Gain of ubiquitination at E28 (P = 0.0117);Gain of ubiquitination at E28 (P = 0.0117);
MVP		0.19
ClinPred		0.88	D
GERP RS		4.2
Varity_R		0.22
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00080
dbscSNV1_RF	Benign	0.050
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

LitVar

Other links and lift over

dbSNP: rs1170316474; hg19: chr2-25314268;