Genetic Variant EIPR1:p.Arg279Gly (chr2-3192568-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003310.5(EIPR1):c.835C>G(p.Arg279Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R279C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EIPR1
NM_003310.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.01

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.862

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.835C>G	p.Arg279Gly	missense	Exon 8 of 9	NP_003301.1	Q53HC9
EIPR1	NM_001330530.3		c.916C>G	p.Arg306Gly	missense	Exon 9 of 10	NP_001317459.1	A8MUM1
EIPR1	NM_001330531.3		c.403C>G	p.Arg135Gly	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.835C>G	p.Arg279Gly	missense	Exon 8 of 9	ENSP00000371559.4	Q53HC9
EIPR1	ENST00000864323.1		c.925C>G	p.Arg309Gly	missense	Exon 9 of 10	ENSP00000534382.1
EIPR1	ENST00000398659.8	TSL:5	c.916C>G	p.Arg306Gly	missense	Exon 9 of 10	ENSP00000381652.4	A8MUM1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459444

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

85946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111440

Other (OTH)

AF:

0.00

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

-0.24

PhyloP100

4.0

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.59

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.90

MutPred

0.64

Loss of stability (P = 0.0511)

MVP

0.89

MPC

1.5

ClinPred

0.99

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.70

gMVP

0.71

Mutation Taster

=30/70

disease causing

(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