3-27718876-G-A

Variant names:

• chr3-27718876-G-A
• rs147676215
• NM_001278182.2:c.1176C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001278182.2(EOMES):​c.1176C>T​(p.Ser392Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000565 in 1,612,780 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (2 hom.)
• Consequence: EOMES NM_001278182.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.20
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly-polymicrogyria-corpus callosum agenesis syndrome

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-27718876-G-A is Benign according to our data. Variant chr3-27718876-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 771851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EOMES	NM_001278182.2	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 6	ENST00000449599.4	NP_001265111.1
EOMES	NM_005442.4	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 6		NP_005433.2
EOMES	NM_001278183.2	c.291C>T	p.Ser97Ser	synonymous_variant	Exon 4 of 6		NP_001265112.1
EOMES	XM_005265510.5	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 7		XP_005265567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EOMES	ENST00000449599.4	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 6	1	NM_001278182.2	ENSP00000388620.1
EOMES	ENST00000295743.8	c.1176C>T	p.Ser392Ser	synonymous_variant	Exon 4 of 6	1		ENSP00000295743.4
EOMES	ENST00000461503.2	c.291C>T	p.Ser97Ser	synonymous_variant	Exon 4 of 6	2		ENSP00000487112.1

Frequencies

GnomAD3 genomes AF: 0.000644 AC: 98 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000741 AC: 186 AN: 250992 AF XY: 0.000870

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000828

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.000557 AC: 813 AN: 1460536 Hom.: 2 Cov.: 31 AF XY: 0.000633 AC XY: 460 AN XY: 726414

African (AFR) AF: 0.000478 AC: 16 AN: 33444

American (AMR) AF: 0.000918 AC: 41 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000859 AC: 74 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.0118 AC: 68 AN: 5764

European-Non Finnish (NFE) AF: 0.000476 AC: 529 AN: 1110984

Other (OTH) AF: 0.000961 AC: 58 AN: 60346

GnomAD4 genome AF: 0.000644 AC: 98 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.000658 AC XY: 49 AN XY: 74448

African (AFR) AF: 0.000144 AC: 6 AN: 41536

American (AMR) AF: 0.00177 AC: 27 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000809 AC: 55 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.000884

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EOMES: BP4, BP7 -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 01, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.8
DANN	Benign	0.78
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs147676215; hg19: chr3-27760367;