Genetic Variant NM_003310.5:c.654-238G>A (chr2-3194404-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003310.5(EIPR1):c.654-238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 367,636 control chromosomes in the GnomAD database, including 138,235 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.86 ( 56580 hom., cov: 30)

Exomes 𝑓: 0.86 ( 81655 hom. )

Consequence

EIPR1
NM_003310.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.446

Publications

3 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
EIPR1	NM_003310.5	MANE Select	c.654-238G>A	intron	N/A	NP_003301.1	Q53HC9
EIPR1	NM_001330530.3		c.735-238G>A	intron	N/A	NP_001317459.1	A8MUM1
EIPR1	NM_001330531.3		c.222-238G>A	intron	N/A	NP_001317460.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EIPR1	ENST00000382125.9	TSL:1 MANE Select	c.654-238G>A	intron	N/A	ENSP00000371559.4	Q53HC9
EIPR1	ENST00000864323.1		c.744-238G>A	intron	N/A	ENSP00000534382.1
EIPR1	ENST00000398659.8	TSL:5	c.735-238G>A	intron	N/A	ENSP00000381652.4	A8MUM1

Frequencies

GnomAD3 genomes

AF:

0.859

AC:

130454

AN:

151932

Hom.:

56544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.813

Gnomad AMI

AF:

0.961

Gnomad AMR

AF:

0.889

Gnomad ASJ

AF:

0.930

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.772

Gnomad FIN

AF:

0.855

Gnomad MID

AF:

0.915

Gnomad NFE

AF:

0.908

Gnomad OTH

AF:

0.876

GnomAD4 exome

AF:

0.863

AC:

186028

AN:

215586

Hom.:

81655

Cov.:

AF XY:

0.863

AC XY:

94931

AN XY:

109948

show subpopulations

African (AFR)

AF:

0.813

AC:

6537

AN:

8042

American (AMR)

AF:

0.900

AC:

8028

AN:

8920

Ashkenazi Jewish (ASJ)

AF:

0.930

AC:

7011

AN:

7536

East Asian (EAS)

AF:

0.514

AC:

9353

AN:

18206

South Asian (SAS)

AF:

0.780

AC:

7032

AN:

9018

European-Finnish (FIN)

AF:

0.869

AC:

11611

AN:

13364

Middle Eastern (MID)

AF:

0.926

AC:

993

AN:

1072

European-Non Finnish (NFE)

AF:

0.911

AC:

123621

AN:

135758

Other (OTH)

AF:

0.866

AC:

11842

AN:

13670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1123

2246

3368

4491

5614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

628

1256

1884

2512

3140

<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

AF:

0.859

AC:

130551

AN:

152050

Hom.:

56580

Cov.:

AF XY:

0.854

AC XY:

63493

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.813

AC:

33697

AN:

41470

American (AMR)

AF:

0.889

AC:

13602

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.930

AC:

3226

AN:

3470

East Asian (EAS)

AF:

0.492

AC:

2518

AN:

5114

South Asian (SAS)

AF:

0.774

AC:

3720

AN:

4808

European-Finnish (FIN)

AF:

0.855

AC:

9037

AN:

10572

Middle Eastern (MID)

AF:

0.912

AC:

268

AN:

294

European-Non Finnish (NFE)

AF:

0.908

AC:

61761

AN:

68012

Other (OTH)

AF:

0.877

AC:

1849

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

904

1808

2712

3616

4520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.896

Hom.:

35401

Bravo

AF:

0.860

Asia WGS

AF:

0.633

AC:

2206

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.19

(source)

DANN

Benign

0.64

PhyloP100

-0.45

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over