chr2-25136581-A-G

Variant names:

• chr2-25136581-A-G
• rs1413477557
• NM_014971.2:c.1543A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014971.2(EFR3B):​c.1543A>G​(p.Thr515Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000838 in 1,551,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: EFR3B NM_014971.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1495404).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFR3B	NM_014971.2	MANE Select	c.1543A>G	p.Thr515Ala	missense	Exon 14 of 23	NP_055786.1	Q9Y2G0-1
	EFR3B	NM_001319099.2		c.1438A>G	p.Thr480Ala	missense	Exon 14 of 23	NP_001306028.1	E7ESK9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFR3B	ENST00000403714.8	TSL:5 MANE Select	c.1543A>G	p.Thr515Ala	missense	Exon 14 of 23	ENSP00000384081.3	Q9Y2G0-1
	EFR3B	ENST00000405108.5	TSL:1	c.1099A>G	p.Thr367Ala	missense	Exon 11 of 20	ENSP00000384454.1	Q9Y2G0-2
	EFR3B	ENST00000858650.1		c.1516A>G	p.Thr506Ala	missense	Exon 14 of 23	ENSP00000528709.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152040 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000715 AC: 10 AN: 1399104 Hom.: 0 Cov.: 31 AF XY: 0.00000580 AC XY: 4 AN XY: 690078

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00000742 AC: 8 AN: 1078802

Other (OTH) AF: 0.0000172 AC: 1 AN: 57978

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152040 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74278

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0084
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.057
Sift	Benign	0.31	T
Sift4G	Benign	0.53	T
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.30		Loss of methylation at K519 (P = 0.056)
MVP		0.048
ClinPred		0.71	D
GERP RS		5.2
Varity_R		0.092
gMVP		0.41
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs1413477557; hg19: chr2-25359450;