rs4778983

Variant names:

• chr15-82210737-T-C
• rs4778983
• NM_024580.6:c.1750+3980A>G

Variant summary

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

The NM_024580.6(EFL1):​c.1750+3980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,650 control chromosomes in the GnomAD database, including 7,828 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 0.31 (7828 hom., cov: 30)
• Consequence: EFL1 NM_024580.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 publications found

Genes affected

EFL1 (HGNC:25789): (elongation factor like GTPase 1) Enables GTPase activity and ribosome binding activity. Involved in GTP metabolic process and mature ribosome assembly. Predicted to be part of ribonucleoprotein complex. Implicated in Shwachman-Diamond syndrome. [provided by Alliance of Genome Resources, Apr 2022]

EFL1 Gene-Disease associations (from GenCC):

• Shwachman-Diamond syndrome 2

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• Shwachman-Diamond syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024580.6. 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
	EFL1	NM_024580.6	MANE Select	c.1750+3980A>G		intron	N/A	NP_078856.4
	EFL1	NM_001322845.2		c.1750+3980A>G		intron	N/A	NP_001309774.1	Q7Z2Z2-1
	EFL1	NM_001040610.3		c.1597+3980A>G		intron	N/A	NP_001035700.1	Q7Z2Z2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFL1	ENST00000268206.12	TSL:1 MANE Select	c.1750+3980A>G		intron	N/A	ENSP00000268206.7	Q7Z2Z2-1
	EFL1	ENST00000359445.8	TSL:1	c.1597+3980A>G		intron	N/A	ENSP00000352418.3	Q7Z2Z2-2
	EFL1	ENST00000956176.1		c.1750+3980A>G		intron	N/A	ENSP00000626235.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47575 AN: 151532 Hom.: 7820 Cov.: 30

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.314 AC: 47619 AN: 151650 Hom.: 7828 Cov.: 30 AF XY: 0.305 AC XY: 22612 AN XY: 74070

African (AFR) AF: 0.386 AC: 15943 AN: 41326

American (AMR) AF: 0.243 AC: 3697 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3466

East Asian (EAS) AF: 0.216 AC: 1107 AN: 5136

South Asian (SAS) AF: 0.152 AC: 728 AN: 4790

European-Finnish (FIN) AF: 0.231 AC: 2437 AN: 10530

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21405 AN: 67856

Other (OTH) AF: 0.311 AC: 656 AN: 2106

Alfa AF: 0.329 Hom.: 1020

Bravo AF: 0.317

Asia WGS AF: 0.195 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		-1.0
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: rs4778983; hg19: chr15-82503078;