Variant chr1-118884636-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001330677.2(TBX15):c.*96C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,124,062 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 22 hom., cov: 31)

Exomes 𝑓: 0.00084 ( 13 hom. )

Consequence

TBX15
NM_001330677.2 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.612

Variant links:

Genes affected

TBX15 (HGNC:11594): (T-box transcription factor 15) This gene belongs to the T-box family of genes, which encode a phylogenetically conserved family of transcription factors that regulate a variety of developmental processes. All these genes contain a common T-box DNA-binding domain. Mutations in this gene are associated with Cousin syndrome.[provided by RefSeq, Oct 2009]

TBX15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-118884636-G-A is Benign according to our data. Variant chr1-118884636-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1208793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00711 (1059/149024) while in subpopulation AFR AF= 0.0251 (1017/40494). AF 95% confidence interval is 0.0238. There are 22 homozygotes in gnomad4. There are 522 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX15	NM_001330677.2 linkuse as main transcript	c.*96C>T		3_prime_UTR_variant	8/8	ENST00000369429.5	NP_001317606.1	Q96SF7-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TBX15	ENST00000369429 linkuse as main transcript	c.*96C>T	3_prime_UTR_variant	8/8	5	NM_001330677.2	ENSP00000358437.3	Q96SF7-1
TBX15	ENST00000207157 linkuse as main transcript	c.*96C>T	3_prime_UTR_variant	8/8	1		ENSP00000207157.3	Q96SF7-2
TBX15	ENST00000449873 linkuse as main transcript	c.*96C>T	3_prime_UTR_variant	4/4	5		ENSP00000398625.1	Q5JT55

Frequencies

GnomAD3 genomes

AF:

0.00712

AC:

1061

AN:

148974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00187

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00654

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00488

GnomAD4 exome

AF:

0.000838

AC:

817

AN:

975038

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

339

AN XY:

498654

show subpopulations

Gnomad4 AFR exome

AF:

0.0312

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000173

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000424

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00711

AC:

1059

AN:

149024

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

522

AN XY:

72532

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.00187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00485

Alfa

AF:

0.00137

Hom.:

Bravo

AF:

0.00794

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 08, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.8

DANN

Benign

0.80

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