Genetic Variant EOMES:p.Ala119_Ala120insGlyAla (chr3-27721936-G-GCGGCGC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6BA1

The NM_001278182.2(EOMES):c.358_359insGCGCCG(p.Ala119_Ala120insGlyAla) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,353,548 control chromosomes in the GnomAD database, including 90,850 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.41 ( 13972 hom., cov: 0)

Exomes 𝑓: 0.38 ( 76878 hom. )

Consequence

EOMES
NM_001278182.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

EOMES (HGNC:3372): (eomesodermin) This gene belongs to the TBR1 (T-box brain protein 1) sub-family of T-box genes that share the common DNA-binding T-box domain. The encoded protein is a transcription factor which is crucial for embryonic development of mesoderm and the central nervous system in vertebrates. The protein may also be necessary for the differentiation of effector CD8+ T cells which are involved in defense against viral infections. A similar gene disrupted in mice is shown to be essential during trophoblast development and gastrulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

EOMES links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001278182.2

BP6

Variant 3-27721936-G-GCGGCGC is Benign according to our data. Variant chr3-27721936-G-GCGGCGC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210936.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOMES	NM_001278182.2 link	c.358_359insGCGCCG	p.Ala119_Ala120insGlyAla	conservative_inframe_insertion	Exon 1 of 6	ENST00000449599.4	NP_001265111.1	O95936-4B7Z4K0
EOMES	NM_005442.4 link	c.358_359insGCGCCG	p.Ala119_Ala120insGlyAla	conservative_inframe_insertion	Exon 1 of 6		NP_005433.2	O95936-1B7Z4K0
EOMES	XM_005265510.5 link	c.358_359insGCGCCG	p.Ala119_Ala120insGlyAla	conservative_inframe_insertion	Exon 1 of 7		XP_005265567.1
EOMES	NM_001278183.2 link	c.-5+493_-5+494insGCGCCG		intron_variant	Intron 1 of 5		NP_001265112.1	O95936-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EOMES	ENST00000449599.4 link	c.358_359insGCGCCG	p.Ala119_Ala120insGlyAla	conservative_inframe_insertion	Exon 1 of 6	1	NM_001278182.2	ENSP00000388620.1	O95936-4
EOMES	ENST00000295743.8 link	c.358_359insGCGCCG	p.Ala119_Ala120insGlyAla	conservative_inframe_insertion	Exon 1 of 6	1		ENSP00000295743.4	O95936-1
EOMES	ENST00000461503.2 link	c.-5+493_-5+494insGCGCCG		intron_variant	Intron 1 of 5	2		ENSP00000487112.1	O95936-3

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62248

AN:

150912

Hom.:

13961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.477

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.293

AC:

7018

AN:

23932

Hom.:

1392

AF XY:

0.304

AC XY:

4316

AN XY:

14176

show subpopulations

Gnomad AFR exome

AF:

0.0904

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.391

Gnomad SAS exome

AF:

0.453

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.377

AC:

452917

AN:

1202526

Hom.:

76878

Cov.:

AF XY:

0.378

AC XY:

221472

AN XY:

585252

show subpopulations

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.520

Gnomad4 ASJ exome

AF:

0.396

Gnomad4 EAS exome

AF:

0.732

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.338

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.401

GnomAD4 genome

AF:

0.412

AC:

62288

AN:

151022

Hom.:

13972

Cov.:

AF XY:

0.420

AC XY:

30986

AN XY:

73736

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.565

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.814

Gnomad4 SAS

AF:

0.680

Gnomad4 FIN

AF:

0.374

Gnomad4 NFE

AF:

0.392

Gnomad4 OTH

AF:

0.428

Alfa

AF:

0.185

Hom.:

310

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Apr 04, 2014

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 17, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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