chr15-48878325-A-C

Position:

chr15-48878325-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014335.3(EID1):c.149A>C(p.Gln50Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,294 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

EID1
NM_014335.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.277

Variant links:

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]

EID1 links:

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]

SHC4 links:

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ACMG classification

Classification made for transcript

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=0.018385768).

BP6

Variant 15-48878325-A-C is Benign according to our data. Variant chr15-48878325-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2315054.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EID1	NM_014335.3 linkuse as main transcript	c.149A>C	p.Gln50Pro	missense_variant	1/1	ENST00000530028.3
SHC4	NM_203349.4 linkuse as main transcript	c.840+5923T>G		intron_variant		ENST00000332408.9
SHC4	XM_005254375.4 linkuse as main transcript	c.291+5923T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EID1	ENST00000530028.3 linkuse as main transcript	c.149A>C	p.Gln50Pro	missense_variant	1/1		NM_014335.3	P1	Q9Y6B2-1
SHC4	ENST00000332408.9 linkuse as main transcript	c.840+5923T>G		intron_variant		1	NM_203349.4	P1	Q6S5L8-1
EID1	ENST00000560490.1 linkuse as main transcript	c.97-14A>C		splice_polypyrimidine_tract_variant, intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248710

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461294

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726882

show subpopulations

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.7

DANN

Benign

0.60

DEOGEN2

Benign

0.013

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.19

M_CAP

Benign

0.0038

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.6

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.39

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.060

MutPred

0.14

Loss of MoRF binding (P = 0.0624);

MVP

0.12

MPC

0.27

ClinPred

0.025

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.063

gMVP

0.038

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over