rs3744262

Variant names:

• chr17-7710447-G-A
• rs3744262
• NM_001406.4:c.*871G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7710447-G-A
• chr17-7710447-G-C
• chr17-7710447-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001406.4(EFNB3):​c.*871G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.447 in 152,598 control chromosomes in the GnomAD database, including 17,526 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 0.45 (17438 hom., cov: 33)
  • Exomes 𝑓: 0.61 (88 hom.)
• Consequence: EFNB3 NM_001406.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• Publications: 10 publications found

Genes affected

EFNB3 (HGNC:3228): (ephrin B3) EFNB3, a member of the ephrin gene family, is important in brain development as well as in its maintenance. Moreover, since levels of EFNB3 expression were particularly high in several forebrain subregions compared to other brain subregions, it may play a pivotal role in forebrain function. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, particularly in the nervous system. EPH Receptors typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee (1997). Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are similarly divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001406.4. 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
	EFNB3	NM_001406.4	MANE Select	c.*871G>A		3_prime_UTR	Exon 5 of 5	NP_001397.1	Q15768

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNB3	ENST00000226091.3	TSL:1 MANE Select	c.*871G>A		3_prime_UTR	Exon 5 of 5	ENSP00000226091.2	Q15768

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67917 AN: 151984 Hom.: 17448 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.469

GnomAD4 exome AF: 0.606 AC: 302 AN: 498 Hom.: 88 Cov.: 0 AF XY: 0.577 AC XY: 179 AN XY: 310

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.616 AC: 260 AN: 422

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.558 AC: 29 AN: 52

Other (OTH) AF: 0.500 AC: 5 AN: 10

GnomAD4 genome AF: 0.446 AC: 67907 AN: 152100 Hom.: 17438 Cov.: 33 AF XY: 0.445 AC XY: 33057 AN XY: 74334

African (AFR) AF: 0.194 AC: 8050 AN: 41476

American (AMR) AF: 0.427 AC: 6527 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1817 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2009 AN: 5172

South Asian (SAS) AF: 0.362 AC: 1747 AN: 4822

European-Finnish (FIN) AF: 0.591 AC: 6248 AN: 10566

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39852 AN: 67992

Other (OTH) AF: 0.465 AC: 983 AN: 2112

Alfa AF: 0.531 Hom.: 35040

Bravo AF: 0.424

Asia WGS AF: 0.326 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.93
PhyloP100		4.5
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: rs3744262; hg19: chr17-7613765; COSMIC: COSV56833530;