rs7799

chr13-40958916-T-C

Variant summary

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

The NM_172373.4(ELF1):c.173A>G(p.Asn58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,613,070 control chromosomes in the GnomAD database, including 348,751 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.54 (25721 hom., cov: 31)
  • Exomes 𝑓: 0.66 (323030 hom.)
• Consequence: ELF1 NM_172373.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

Genes affected

ELF1 (HGNC:3316): (E74 like ETS transcription factor 1) This gene encodes an E26 transformation-specific related transcription factor. The encoded protein is primarily expressed in lymphoid cells and acts as both an enhancer and a repressor to regulate transcription of various genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8838622E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELF1	NM_172373.4	c.173A>G	p.Asn58Ser	missense_variant	3/9	ENST00000239882.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELF1	ENST00000239882.7	c.173A>G	p.Asn58Ser	missense_variant	3/9	1	NM_172373.4	P1
ELF1	ENST00000635415.1	c.173A>G	p.Asn58Ser	missense_variant	3/9	5
ELF1	ENST00000625359.1	c.173A>G	p.Asn58Ser	missense_variant	2/8	2
ELF1	ENST00000498824.4	c.173A>G	p.Asn58Ser	missense_variant, NMD_transcript_variant	2/9	2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82762 AN: 151838 Hom.: 25729 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.581

GnomAD3 exomes AF: 0.614 AC: 154113 AN: 250868 Hom.: 50931 AF XY: 0.624 AC XY: 84564 AN XY: 135622

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.644

Gnomad EAS exome AF: 0.185

Gnomad SAS exome AF: 0.594

Gnomad FIN exome AF: 0.706

Gnomad NFE exome AF: 0.696

Gnomad OTH exome AF: 0.637

GnomAD4 exome AF: 0.656 AC: 957817 AN: 1461114 Hom.: 323030 Cov.: 56 AF XY: 0.655 AC XY: 476350 AN XY: 726868

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.702

Gnomad4 NFE exome AF: 0.688

Gnomad4 OTH exome AF: 0.610

GnomAD4 genome AF: 0.545 AC: 82756 AN: 151956 Hom.: 25721 Cov.: 31 AF XY: 0.549 AC XY: 40740 AN XY: 74242

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.573

Alfa AF: 0.656 Hom.: 87437

Bravo AF: 0.530

TwinsUK AF: 0.679 AC: 2518

ALSPAC AF: 0.679 AC: 2618

ESP6500AA AF: 0.257 AC: 1133

ESP6500EA AF: 0.690 AC: 5931

ExAC AF: 0.608 AC: 73757

Asia WGS AF: 0.339 AC: 1178 AN: 3478

EpiCase AF: 0.694

EpiControl AF: 0.698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	11
Dann	Uncertain	0.98
DEOGEN2	Benign	0.10	T;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.85	D;D;D
MetaRNN	Benign	0.0000029	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.
MutationTaster	Benign	0.79	P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N;.;.
REVEL	Benign	0.068
Sift	Benign	0.17	T;.;.
Sift4G	Benign	0.27	T;T;.
Polyphen		0.015	B;.;.
Vest4		0.037
MPC		0.13
ClinPred		0.0055	T
GERP RS		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.038
gMVP		0.22

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: rs7799; hg19: chr13-41533052; COSMIC: COSV53497107;