2-25154307-T-C

Variant names:

• chr2-25154307-T-C
• rs2164808
• NM_014971.2:c.2421T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 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 -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 rank	MANE	Protein	UniProt
EFR3B	NM_014971.2	c.2421T>C	p.Tyr807Tyr	synonymous_variant	Exon 23 of 23	ENST00000403714.8	NP_055786.1
EFR3B	NM_001319099.2	c.2316T>C	p.Tyr772Tyr	synonymous_variant	Exon 23 of 23		NP_001306028.1

Ensembl

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

GnomAD2 exomes AF: 0.668 AC: 105497 AN: 157944 AF XY: 0.660

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 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

African (AFR) AF: 0.857 AC: 27087 AN: 31598

American (AMR) AF: 0.814 AC: 29052 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 14285 AN: 25178

East Asian (EAS) AF: 0.983 AC: 35131 AN: 35736

South Asian (SAS) AF: 0.695 AC: 55085 AN: 79232

European-Finnish (FIN) AF: 0.585 AC: 28902 AN: 49436

Middle Eastern (MID) AF: 0.618 AC: 3523 AN: 5700

European-Non Finnish (NFE) AF: 0.551 AC: 594698 AN: 1078924

Other (OTH) AF: 0.625 AC: 36334 AN: 58114

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

African (AFR) AF: 0.847 AC: 35182 AN: 41524

American (AMR) AF: 0.760 AC: 11611 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1951 AN: 3464

East Asian (EAS) AF: 0.989 AC: 5117 AN: 5176

South Asian (SAS) AF: 0.738 AC: 3555 AN: 4820

European-Finnish (FIN) AF: 0.602 AC: 6355 AN: 10560

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37464 AN: 67986

Other (OTH) AF: 0.675 AC: 1428 AN: 2114

Alfa AF: 0.610 Hom.: 49049

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
PhyloP100		-1.0
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2164808; hg19: chr2-25377176; COSMIC: COSV53120184;