NM_014335.3:c.49C>A

Variant names:

• chr15-48878225-C-A
• rs771216755
• NM_014335.3:c.49C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014335.3(EID1):​c.49C>A​(p.Leu17Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: EID1 NM_014335.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965

Genes affected

EID1 (HGNC:1191): (EP300 interacting inhibitor of differentiation 1) Enables histone acetyltransferase binding activity and histone acetyltransferase regulator activity. Involved in cell differentiation and negative regulation of transcription, DNA-templated. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in cytoplasmic ribonucleoprotein granule and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SHC4 (HGNC:16743): (SHC adaptor protein 4) Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within several processes, including apoptotic process; positive regulation of cell population proliferation; and stem cell differentiation. Predicted to be located in postsynaptic membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12978539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EID1	NM_014335.3	c.49C>A	p.Leu17Met	missense_variant	Exon 1 of 1	ENST00000530028.3	NP_055150.1
SHC4	NM_203349.4	c.840+6023G>T		intron_variant	Intron 4 of 11	ENST00000332408.9	NP_976224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EID1	ENST00000530028.3	c.49C>A	p.Leu17Met	missense_variant	Exon 1 of 1	6	NM_014335.3	ENSP00000431162.2
SHC4	ENST00000332408.9	c.840+6023G>T		intron_variant	Intron 4 of 11	1	NM_203349.4	ENSP00000329668.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1452400 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721514

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000542

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T;T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;T
Polyphen		0.95	P;.
Vest4		0.31
MutPred		0.18		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.26
MPC		0.73
ClinPred		0.89	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.059

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs771216755; hg19: chr15-49170422;