rs114913626

Variant names:

• chr14-23118858-G-A
• rs114913626
• NM_001805.4:c.234C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001805.4(CEBPE):​c.234C>T​(p.Pro78Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,614,018 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (16 hom.)
• Consequence: CEBPE NM_001805.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

Genes affected

CEBPE (HGNC:1836): (CCAAT enhancer binding protein epsilon) The protein encoded by this gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related protein CEBP-delta. The encoded protein may be essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells. Mutations in this gene have been associated with Specific Granule Deficiency, a rare congenital disorder. Multiple variants of this gene have been described, but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

CEBPE Gene-Disease associations (from GenCC):

• specific granule deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• specific granule deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000295888 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 14-23118858-G-A is Benign according to our data. Variant chr14-23118858-G-A is described in ClinVar as Benign. ClinVar VariationId is 530669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.43 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00776 (1181/152274) while in subpopulation AFR AF = 0.0267 (1110/41554). AF 95% confidence interval is 0.0254. There are 13 homozygotes in GnomAd4. There are 553 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001805.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPE	NM_001805.4	MANE Select	c.234C>T	p.Pro78Pro	synonymous	Exon 1 of 2	NP_001796.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEBPE	ENST00000206513.6	TSL:1 MANE Select	c.234C>T	p.Pro78Pro	synonymous	Exon 1 of 2	ENSP00000206513.5
	CEBPE	ENST00000696121.1		n.262-59C>T		intron	N/A
	CEBPE	ENST00000696122.1		n.43-63C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00779 AC: 1186 AN: 152156 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00205 AC: 514 AN: 250726 AF XY: 0.00147

Gnomad AFR exome AF: 0.0278

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.000833 AC: 1217 AN: 1461744 Hom.: 16 Cov.: 32 AF XY: 0.000715 AC XY: 520 AN XY: 727174

African (AFR) AF: 0.0289 AC: 966 AN: 33462

American (AMR) AF: 0.00157 AC: 70 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5756

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1111964

Other (OTH) AF: 0.00190 AC: 115 AN: 60388

GnomAD4 genome AF: 0.00776 AC: 1181 AN: 152274 Hom.: 13 Cov.: 32 AF XY: 0.00743 AC XY: 553 AN XY: 74452

African (AFR) AF: 0.0267 AC: 1110 AN: 41554

American (AMR) AF: 0.00320 AC: 49 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68004

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00733 Hom.: 15

Bravo AF: 0.00856

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Specific granule deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.8
DANN	Benign	0.87
PhyloP100		1.4
PromoterAI		-0.059	Neutral
Mutation Taster		=100/0	polymorphism

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: rs114913626; hg19: chr14-23588067;