rs1422668

Variant names:

• chr5-159079126-A-G
• rs1422668
• NM_024007.5:c.485+5540T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024007.5(EBF1):​c.485+5540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,014 control chromosomes in the GnomAD database, including 6,754 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 0.29 (6754 hom., cov: 31)
• Consequence: EBF1 NM_024007.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBF1	NM_024007.5	c.485+5540T>C		intron_variant	Intron 5 of 15	ENST00000313708.11	NP_076870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF1	ENST00000313708.11	c.485+5540T>C		intron_variant	Intron 5 of 15	1	NM_024007.5	ENSP00000322898.6

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44489 AN: 151896 Hom.: 6756 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44496 AN: 152014 Hom.: 6754 Cov.: 31 AF XY: 0.286 AC XY: 21280 AN XY: 74314

African (AFR) AF: 0.283 AC: 11711 AN: 41446

American (AMR) AF: 0.220 AC: 3360 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1392 AN: 3470

East Asian (EAS) AF: 0.164 AC: 843 AN: 5146

South Asian (SAS) AF: 0.237 AC: 1140 AN: 4820

European-Finnish (FIN) AF: 0.306 AC: 3231 AN: 10560

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21874 AN: 67962

Other (OTH) AF: 0.274 AC: 579 AN: 2114

Alfa AF: 0.297 Hom.: 2648

Bravo AF: 0.285

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.30
PhyloP100		0.21
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: rs1422668; hg19: chr5-158506134; COSMIC: COSV58172187;