chr2-25154307-T-C

Position:

• chr2-25154307-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014971.2(EFR3B):​c.2421T>C​(p.Tyr807Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,551,756 control chromosomes in the GnomAD database, including 286,432 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 0.68 (36716 hom., cov: 32)
  • Exomes 𝑓: 0.59 (249716 hom.)
• Consequence: EFR3B NM_014971.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFR3B	NM_014971.2	c.2421T>C	p.Tyr807Tyr	synonymous_variant	23/23	ENST00000403714.8	NP_055786.1
EFR3B	NM_001319099.2	c.2316T>C	p.Tyr772Tyr	synonymous_variant	23/23		NP_001306028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFR3B	ENST00000403714.8	c.2421T>C	p.Tyr807Tyr	synonymous_variant	23/23	5	NM_014971.2	ENSP00000384081.3
EFR3B	ENST00000405108.5	c.1977T>C	p.Tyr659Tyr	synonymous_variant	20/20	1		ENSP00000384454.1
EFR3B	ENST00000402191.5	c.2316T>C	p.Tyr772Tyr	synonymous_variant	23/23	5		ENSP00000385832.1
EFR3B	ENST00000264719.5	c.1926T>C	p.Tyr642Tyr	synonymous_variant	18/18	5		ENSP00000264719.5

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103330 AN: 152016 Hom.: 36660 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.672

GnomAD3 exomes AF: 0.668 AC: 105497 AN: 157944 Hom.: 36940 AF XY: 0.660 AC XY: 55013 AN XY: 83386

Gnomad AFR exome AF: 0.855

Gnomad AMR exome AF: 0.821

Gnomad ASJ exome AF: 0.566

Gnomad EAS exome AF: 0.998

Gnomad SAS exome AF: 0.698

Gnomad FIN exome AF: 0.588

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.634

GnomAD4 exome AF: 0.589 AC: 824097 AN: 1399622 Hom.: 249716 Cov.: 54 AF XY: 0.590 AC XY: 407031 AN XY: 690324

Gnomad4 AFR exome AF: 0.857

Gnomad4 AMR exome AF: 0.814

Gnomad4 ASJ exome AF: 0.567

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.585

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.680 AC: 103446 AN: 152134 Hom.: 36716 Cov.: 32 AF XY: 0.690 AC XY: 51319 AN XY: 74368

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.738

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.675

Alfa AF: 0.585 Hom.: 34270

Bravo AF: 0.703

Asia WGS AF: 0.861 AC: 2994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.38
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2164808; hg19: chr2-25377176; COSMIC: COSV53120184;