NM_014971.2:c.212+46T>C

Variant names:

• chr2-25093176-T-C
• rs10495751
• NM_014971.2:c.212+46T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014971.2(EFR3B):​c.212+46T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,544,070 control chromosomes in the GnomAD database, including 5,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (2373 hom., cov: 32)
  • Exomes 𝑓: 0.037 (2654 hom.)
• Consequence: EFR3B NM_014971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFR3B	NM_014971.2	MANE Select	c.212+46T>C		intron	N/A	NP_055786.1
	EFR3B	NM_001319099.2		c.107+46T>C		intron	N/A	NP_001306028.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFR3B	ENST00000403714.8	TSL:5 MANE Select	c.212+46T>C		intron	N/A	ENSP00000384081.3
	EFR3B	ENST00000402191.5	TSL:5	c.107+46T>C		intron	N/A	ENSP00000385832.1
	EFR3B	ENST00000401432.7	TSL:2	c.212+46T>C		intron	N/A	ENSP00000386082.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17079 AN: 152018 Hom.: 2365 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.0410

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0833

GnomAD2 exomes AF: 0.0475 AC: 7355 AN: 154774 AF XY: 0.0452

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.0262

Gnomad ASJ exome AF: 0.0472

Gnomad EAS exome AF: 0.000461

Gnomad FIN exome AF: 0.0167

Gnomad NFE exome AF: 0.0285

Gnomad OTH exome AF: 0.0395

GnomAD4 exome AF: 0.0372 AC: 51748 AN: 1391934 Hom.: 2654 Cov.: 30 AF XY: 0.0369 AC XY: 25328 AN XY: 685742

African (AFR) AF: 0.347 AC: 10869 AN: 31344

American (AMR) AF: 0.0304 AC: 1068 AN: 35178

Ashkenazi Jewish (ASJ) AF: 0.0462 AC: 1154 AN: 24954

East Asian (EAS) AF: 0.000337 AC: 12 AN: 35612

South Asian (SAS) AF: 0.0560 AC: 4411 AN: 78790

European-Finnish (FIN) AF: 0.0161 AC: 771 AN: 47816

Middle Eastern (MID) AF: 0.0548 AC: 311 AN: 5680

European-Non Finnish (NFE) AF: 0.0282 AC: 30269 AN: 1074756

Other (OTH) AF: 0.0499 AC: 2883 AN: 57804

GnomAD4 genome AF: 0.112 AC: 17102 AN: 152136 Hom.: 2373 Cov.: 32 AF XY: 0.108 AC XY: 8072 AN XY: 74400

African (AFR) AF: 0.331 AC: 13716 AN: 41440

American (AMR) AF: 0.0462 AC: 707 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0410 AC: 142 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5168

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4822

European-Finnish (FIN) AF: 0.0131 AC: 139 AN: 10610

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0271 AC: 1845 AN: 68020

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

Alfa AF: 0.0572 Hom.: 2576

Bravo AF: 0.126

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.52
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs10495751; hg19: chr2-25316045;