13-40958916-T-C

Variant names:

• chr13-40958916-T-C
• rs7799
• NM_172373.4:c.173A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 48 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172373.4. 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
	ELF1	NM_172373.4	MANE Select	c.173A>G	p.Asn58Ser	missense	Exon 3 of 9	NP_758961.1
	ELF1	NM_001370330.1		c.173A>G	p.Asn58Ser	missense	Exon 3 of 9	NP_001357259.1
	ELF1	NM_001370331.1		c.173A>G	p.Asn58Ser	missense	Exon 3 of 9	NP_001357260.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELF1	ENST00000239882.7	TSL:1 MANE Select	c.173A>G	p.Asn58Ser	missense	Exon 3 of 9	ENSP00000239882.3
	ELF1	ENST00000635415.1	TSL:5	c.173A>G	p.Asn58Ser	missense	Exon 3 of 9	ENSP00000489586.1
	ELF1	ENST00000625359.1	TSL:2	c.173A>G	p.Asn58Ser	missense	Exon 2 of 8	ENSP00000486912.1

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

GnomAD2 exomes AF: 0.614 AC: 154113 AN: 250868 AF XY: 0.624

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 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

African (AFR) AF: 0.249 AC: 8322 AN: 33460

American (AMR) AF: 0.692 AC: 30829 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 16675 AN: 26106

East Asian (EAS) AF: 0.192 AC: 7635 AN: 39678

South Asian (SAS) AF: 0.593 AC: 51030 AN: 86126

European-Finnish (FIN) AF: 0.702 AC: 37480 AN: 53392

Middle Eastern (MID) AF: 0.642 AC: 3702 AN: 5766

European-Non Finnish (NFE) AF: 0.688 AC: 765308 AN: 1111684

Other (OTH) AF: 0.610 AC: 36836 AN: 60360

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

African (AFR) AF: 0.254 AC: 10532 AN: 41438

American (AMR) AF: 0.654 AC: 9982 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2216 AN: 3470

East Asian (EAS) AF: 0.183 AC: 941 AN: 5156

South Asian (SAS) AF: 0.570 AC: 2740 AN: 4810

European-Finnish (FIN) AF: 0.715 AC: 7549 AN: 10554

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.687 AC: 46685 AN: 67960

Other (OTH) AF: 0.573 AC: 1207 AN: 2108

Alfa AF: 0.635 Hom.: 124043

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 v4.9

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
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0000029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.045
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.068
Sift	Benign	0.17	T
Sift4G	Benign	0.27	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
Mutation Taster		=99/1	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: rs7799; hg19: chr13-41533052; COSMIC: COSV53497107;