Genetic Variant EIPR1:p.Ile305Val (chr2-3192490-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003310.5(EIPR1):c.913A>G(p.Ile305Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I305F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EIPR1
NM_003310.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.77

Publications

0 publications found

Variant links:

Genes affected

EIPR1 (HGNC:12383): (EARP complex and GARP complex interacting protein 1) This gene has been reported in PMID 9403053 as one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. Alignment of this gene to genomic sequence data suggests that this gene resides on chromosome 2 rather than chromosome 11. [provided by RefSeq, Dec 2008]

EIPR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28946543).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003310.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIPR1	NM_003310.5	MANE Select	c.913A>G	p.Ile305Val	missense	Exon 8 of 9	NP_003301.1	Q53HC9
EIPR1	NM_001330530.3		c.994A>G	p.Ile332Val	missense	Exon 9 of 10	NP_001317459.1	A8MUM1
EIPR1	NM_001330531.3		c.481A>G	p.Ile161Val	missense	Exon 7 of 8	NP_001317460.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIPR1	ENST00000382125.9	TSL:1 MANE Select	c.913A>G	p.Ile305Val	missense	Exon 8 of 9	ENSP00000371559.4	Q53HC9
EIPR1	ENST00000864323.1		c.1003A>G	p.Ile335Val	missense	Exon 9 of 10	ENSP00000534382.1
EIPR1	ENST00000398659.8	TSL:5	c.994A>G	p.Ile332Val	missense	Exon 9 of 10	ENSP00000381652.4	A8MUM1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460794

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726674

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52810

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111784

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.031

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.069

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.59

PhyloP100

7.8

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.39

REVEL

Benign

0.16

Sift

Benign

0.26

Sift4G

Benign

0.56

Polyphen

0.30

Vest4

0.59

MutPred

0.30

Gain of catalytic residue at I305 (P = 0.0058)

MVP

0.69

MPC

0.71

ClinPred

0.84

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.098

gMVP

0.14

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over