rs16990748

Positions:

• chrX-68841386-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004429.5(EFNB1):​c.*732A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 107,250 control chromosomes in the GnomAD database, including 64 homozygotes. There are 817 hemizygotes in GnomAD. 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 0.027 (64 hom., 817 hem., cov: 21)
  • Exomes 𝑓: 0.086 (9 hom. 7 hem.)
  • Failed GnomAD Quality Control
• Consequence: EFNB1 NM_004429.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352

Genes affected

EFNB1 (HGNC:3226): (ephrin B1) The protein encoded by this gene is a type I membrane protein and a ligand of Eph-related receptor tyrosine kinases. It may play a role in cell adhesion and function in the development or maintenance of the nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB1	NM_004429.5	c.*732A>C		3_prime_UTR_variant	5/5	ENST00000204961.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB1	ENST00000204961.5	c.*732A>C		3_prime_UTR_variant	5/5	1	NM_004429.5	P1

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 2921 AN: 107209 Hom.: 64 Cov.: 21 AF XY: 0.0266 AC XY: 814 AN XY: 30649

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.00151

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.00969

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.00606

Gnomad OTH AF: 0.0172

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0861 AC: 29 AN: 337 Hom.: 9 Cov.: 0 AF XY: 0.0483 AC XY: 7 AN XY: 145

Gnomad4 AFR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.0153

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0273 AC: 2924 AN: 107250 Hom.: 64 Cov.: 21 AF XY: 0.0266 AC XY: 817 AN XY: 30696

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0404

Gnomad4 FIN AF: 0.00969

Gnomad4 NFE AF: 0.00607

Gnomad4 OTH AF: 0.0183

Alfa AF: 0.556 Hom.: 2297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs16990748; hg19: chrX-68061229; COSMIC: COSV52662649;