chr3-27721936-G-GCGC

Position:

• chr3-27721936-G-GCGC

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_001278182.2(EOMES):​c.358_359insGCG​(p.Ala119_Ala120insGly) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A120A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EOMES NM_001278182.2 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001278182.2
• BP6: Variant 3-27721936-G-GCGC is Benign according to our data. Variant chr3-27721936-G-GCGC is described in ClinVar as [Benign]. Clinvar id is 771348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EOMES	NM_001278182.2	c.358_359insGCG	p.Ala119_Ala120insGly	inframe_insertion	1/6	ENST00000449599.4
EOMES	NM_005442.4	c.358_359insGCG	p.Ala119_Ala120insGly	inframe_insertion	1/6
EOMES	XM_005265510.5	c.358_359insGCG	p.Ala119_Ala120insGly	inframe_insertion	1/7
EOMES	NM_001278183.2	c.-5+493_-5+494insGCG		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EOMES	ENST00000449599.4	c.358_359insGCG	p.Ala119_Ala120insGly	inframe_insertion	1/6	1	NM_001278182.2	A1
EOMES	ENST00000295743.8	c.358_359insGCG	p.Ala119_Ala120insGly	inframe_insertion	1/6	1		P4
EOMES	ENST00000461503.2	c.-5+493_-5+494insGCG		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000927 AC: 14 AN: 150988 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000959

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.000482

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000999 AC: 1169 AN: 1170716 Hom.: 0 Cov.: 35 AF XY: 0.00126 AC XY: 720 AN XY: 569744

Gnomad4 AFR exome AF: 0.000258

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.000786

Gnomad4 EAS exome AF: 0.000925

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.00168

Gnomad4 NFE exome AF: 0.000543

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.0000927 AC: 14 AN: 151098 Hom.: 0 Cov.: 0 AF XY: 0.0000678 AC XY: 5 AN XY: 73778

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000959

Gnomad4 NFE AF: 0.000163

Gnomad4 OTH AF: 0.000477

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553745484; hg19: chr3-27763427;