rs765652835

Variant names:

• chr2-25121764-C-G
• rs765652835
• NM_014971.2:c.455C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-25121764-C-G
• chr2-25121764-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014971.2(EFR3B):​c.455C>G​(p.Ser152Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S152L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EFR3B NM_014971.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.82
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024149537).

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.455C>G	p.Ser152Trp	missense	Exon 5 of 23	NP_055786.1	Q9Y2G0-1
	EFR3B	NM_001319099.2		c.350C>G	p.Ser117Trp	missense	Exon 5 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.455C>G	p.Ser152Trp	missense	Exon 5 of 23	ENSP00000384081.3	Q9Y2G0-1
	EFR3B	ENST00000405108.5	TSL:1	c.11C>G	p.Ser4Trp	missense	Exon 2 of 20	ENSP00000384454.1	Q9Y2G0-2
	EFR3B	ENST00000858650.1		c.455C>G	p.Ser152Trp	missense	Exon 5 of 23	ENSP00000528709.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000897 AC: 14 AN: 156140 AF XY: 0.0000242

Gnomad AFR exome AF: 0.000512

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000181

Gnomad NFE exome AF: 0.0000992

Gnomad OTH exome AF: 0.000228

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.15e-7 AC: 1 AN: 1399336 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690176

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078976

Other (OTH) AF: 0.00 AC: 0 AN: 58004

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00200 AC: 51

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.024	T
MetaSVM	Uncertain	0.098	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.40		Loss of disorder (P = 1e-04)
MVP		0.42
ClinPred		0.18	T
GERP RS		3.6
PromoterAI		0.014	Neutral
Varity_R		0.79
gMVP		0.92
Mutation Taster		=74/26	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: rs765652835; hg19: chr2-25344633;