13-40933435-T-G

Variant names:

• chr13-40933435-T-G
• NM_172373.4:c.1850A>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_172373.4(ELF1):​c.1850A>C​(p.Asn617Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ELF1 NM_172373.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.717

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0721046).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELF1	NM_172373.4	c.1850A>C	p.Asn617Thr	missense_variant	Exon 9 of 9	ENST00000239882.7	NP_758961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELF1	ENST00000239882.7	c.1850A>C	p.Asn617Thr	missense_variant	Exon 9 of 9	1	NM_172373.4	ENSP00000239882.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1457442 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 724550

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1850A>C (p.N617T) alteration is located in exon 9 (coding exon 8) of the ELF1 gene. This alteration results from a A to C substitution at nucleotide position 1850, causing the asparagine (N) at amino acid position 617 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.3
DANN	Benign	0.93
DEOGEN2	Benign	0.069	T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.62	N;.
REVEL	Benign	0.087
Sift	Uncertain	0.013	D;.
Sift4G	Benign	0.076	T;T
Polyphen		0.062	B;.
Vest4		0.22
MutPred		0.14		Gain of glycosylation at N617 (P = 0.0539);.;
MVP		0.23
MPC		0.19
ClinPred		0.073	T
GERP RS		-2.4
Varity_R		0.091
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-41507571;