15-48878416-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014335.3(EID1):c.240C>A(p.Asn80Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,611,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: EID1 NM_014335.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052749187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EID1	NM_014335.3	c.240C>A	p.Asn80Lys	missense_variant	1/1	ENST00000530028.3
SHC4	NM_203349.4	c.840+5832G>T		intron_variant		ENST00000332408.9
SHC4	XM_005254375.4	c.291+5832G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EID1	ENST00000530028.3	c.240C>A	p.Asn80Lys	missense_variant	1/1		NM_014335.3	P1
SHC4	ENST00000332408.9	c.840+5832G>T		intron_variant		1	NM_203349.4	P1
EID1	ENST00000560490.1	c.174C>A	p.Asn58Lys	missense_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000165 AC: 4 AN: 243072 Hom.: 0 AF XY: 0.00000757 AC XY: 1 AN XY: 132048

Gnomad AFR exome AF: 0.0000676

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000171

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459616 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725910

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74380

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2021

The c.240C>A (p.N80K) alteration is located in exon 1 (coding exon 1) of the EID1 gene. This alteration results from a C to A substitution at nucleotide position 240, causing the asparagine (N) at amino acid position 80 to be replaced by a lysine (K). 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	0.091
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	14
Dann	Benign	0.97
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.30	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.023
Sift	Benign	0.13	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.034	B;.
Vest4		0.051
MutPred		0.23		Gain of ubiquitination at N80 (P = 0.0048);.;
MVP		0.37
MPC		0.25
ClinPred		0.032	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.064
gMVP		0.025

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: rs762791119; hg19: chr15-49170613;