rs6895454

Positions:

• chr5-159096159-C-T

Variant summary

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

The ENST00000313708.11(EBF1):​c.355+184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 636,854 control chromosomes in the GnomAD database, including 6,276 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 0.14 (1950 hom., cov: 33)
  • Exomes 𝑓: 0.11 (4326 hom.)
• Consequence: EBF1 ENST00000313708.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

Genes affected

EBF1 (HGNC:3126): (EBF transcription factor 1) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF1	NM_024007.5	c.355+184G>A		intron_variant		ENST00000313708.11	NP_076870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF1	ENST00000313708.11	c.355+184G>A		intron_variant		1	NM_024007.5	ENSP00000322898	P1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20760 AN: 152064 Hom.: 1954 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.106 AC: 51203 AN: 484672 Hom.: 4326 AF XY: 0.104 AC XY: 26483 AN XY: 254482

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.0845

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.0796

Gnomad4 NFE exome AF: 0.0743

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.137 AC: 20780 AN: 152182 Hom.: 1950 Cov.: 33 AF XY: 0.137 AC XY: 10211 AN XY: 74406

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0842

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0766

Gnomad4 NFE AF: 0.0749

Gnomad4 OTH AF: 0.121

Alfa AF: 0.114 Hom.: 227

Bravo AF: 0.150

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.2
DANN	Benign	0.81

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: rs6895454; hg19: chr5-158523167; COSMIC: COSV58185673; COSMIC: COSV58185673;