Genetic Variant TERB1:p.Pro494Pro (chr16-66770100-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001136505.2(TERB1):c.1482G>A(p.Pro494Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,552,058 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 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

TERB1
NM_001136505.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.901

Variant links:

Genes affected

TERB1 (HGNC:26675): (telomere repeat binding bouquet formation protein 1) Predicted to be involved in homologous chromosome pairing at meiosis and meiotic attachment of telomere to nuclear envelope. Predicted to be located in chromosome, telomeric region and nuclear inner membrane. Predicted to colocalize with shelterin complex. [provided by Alliance of Genome Resources, Apr 2022]

TERB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-66770100-C-T is Benign according to our data. Variant chr16-66770100-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388112.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.901 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
TERB1	NM_001136505.2 link	c.1482G>A	p.Pro494Pro	synonymous_variant	Exon 14 of 19	ENST00000433154.6	NP_001129977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TERB1	ENST00000433154.6 link	c.1482G>A	p.Pro494Pro	synonymous_variant	Exon 14 of 19	5	NM_001136505.2	ENSP00000463762.1	Q8NA31-1
TERB1	ENST00000558713.6 link	c.1482G>A	p.Pro494Pro	synonymous_variant	Exon 13 of 18	5		ENSP00000462883.1	Q8NA31-1
TERB1	ENST00000313294.7 link	n.1356G>A		non_coding_transcript_exon_variant	Exon 13 of 16	5		ENSP00000464579.1	Q8NA31-3
TERB1	ENST00000561333.1 link	n.1713G>A		non_coding_transcript_exon_variant	Exon 14 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000575

AC:

AN:

158258

Hom.:

AF XY:

0.000587

AC XY:

AN XY:

83488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00624

Gnomad SAS exome

AF:

0.000483

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000130

Gnomad OTH exome

AF:

0.000667

GnomAD4 exome

AF:

0.000184

AC:

257

AN:

1399778

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

132

AN XY:

690354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00255

Gnomad4 SAS exome

AF:

0.000316

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000992

Gnomad4 OTH exome

AF:

0.000310

GnomAD4 genome

AF:

0.000230

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000246

Hom.:

Bravo

AF:

0.000348

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TERB1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

DANN

Benign

0.41

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

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