Genetic Variant ENST00000756907.1:n.186C>A (chr22-41381096-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000756907.1(ENSG00000298609):n.186C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,126 control chromosomes in the GnomAD database, including 44,631 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 0.76 ( 44631 hom., cov: 32)

Consequence

ENSG00000298609
ENST00000756907.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.432

Publications

26 publications found

Variant links:

Genes affected

ENSG00000298609 (HGNC:):

ENSG00000298609 links:

TEF (HGNC:11722): (TEF transcription factor, PAR bZIP family member) This gene encodes a member of the PAR (proline and acidic amino acid-rich) subfamily of basic region/leucine zipper (bZIP) transcription factors. It is expressed in a broad range of cells and tissues in adult animals, however, during embryonic development, TEF expression appears to be restricted to the developing anterior pituitary gland, coincident with the appearance of thyroid-stimulating hormone, beta (TSHB). Indeed, TEF can bind to, and transactivate the TSHB promoter. It shows homology (in the functional domains) with other members of the PAR-bZIP subfamily of transcription factors, which include albumin D box-binding protein (DBP), human hepatic leukemia factor (HLF) and chicken vitellogenin gene-binding protein (VBP); VBP is considered the chicken homologue of TEF. Different members of the subfamily can readily form heterodimers, and share DNA-binding, and transcriptional regulatory properties. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

TEF 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=-0.59).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEF	NM_001145398.3 link	c.68-6255G>T		intron_variant	Intron 1 of 3		NP_001138870.1	Q10587-2
LOC105373042	XR_938271.3 link	n.172+644C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000298609	ENST00000756907.1 link	n.186C>A		non_coding_transcript_exon_variant	Exon 1 of 5
TEF	ENST00000406644.7 link	c.68-6255G>T		intron_variant	Intron 1 of 3	2		ENSP00000385256.3		Q10587-2

Frequencies

GnomAD3 genomes

AF:

0.762

AC:

115788

AN:

152008

Hom.:

44579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.854

Gnomad AMI

AF:

0.741

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.754

Gnomad FIN

AF:

0.693

Gnomad MID

AF:

0.723

Gnomad NFE

AF:

0.703

Gnomad OTH

AF:

0.740

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.762

AC:

115894

AN:

152126

Hom.:

44631

Cov.:

AF XY:

0.764

AC XY:

56853

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.854

AC:

35456

AN:

41526

American (AMR)

AF:

0.811

AC:

12411

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.770

AC:

2674

AN:

3472

East Asian (EAS)

AF:

0.805

AC:

4151

AN:

5156

South Asian (SAS)

AF:

0.755

AC:

3642

AN:

4826

European-Finnish (FIN)

AF:

0.693

AC:

7317

AN:

10566

Middle Eastern (MID)

AF:

0.719

AC:

210

AN:

292

European-Non Finnish (NFE)

AF:

0.703

AC:

47814

AN:

67972

Other (OTH)

AF:

0.732

AC:

1549

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1401

2802

4204

5605

7006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.725

Hom.:

67095

Bravo

AF:

0.775

Asia WGS

AF:

0.710

AC:

2472

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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ENST00000756907.1:n.186C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over