Variant chr16-30091070-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_004608.4(TBX6):c.118+6C>T variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.0287 in 1,584,626 control chromosomes in the GnomAD database, including 780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 45 hom., cov: 32)

Exomes 𝑓: 0.029 ( 735 hom. )

Consequence

TBX6
NM_004608.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.0003351

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.68

Variant links:

Genes affected

TBX6 (HGNC:11605): (T-box transcription factor 6) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Knockout studies in mice indicate that this gene is important for specification of paraxial mesoderm structures. [provided by RefSeq, Aug 2008]

TBX6 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=-0.78).

BP6

Variant 16-30091070-G-A is Benign according to our data. Variant chr16-30091070-G-A is described in ClinVar as [Benign]. Clinvar id is 259447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30091070-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0227 (3456/152296) while in subpopulation NFE AF= 0.0348 (2365/67998). AF 95% confidence interval is 0.0336. There are 45 homozygotes in gnomad4. There are 1715 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TBX6	NM_004608.4 linkuse as main transcript	c.118+6C>T	splice_donor_region_variant, intron_variant	ENST00000395224.7
TBX6	XM_011545926.4 linkuse as main transcript	c.118+6C>T	splice_donor_region_variant, intron_variant
TBX6	XM_047434551.1 linkuse as main transcript	c.118+6C>T	splice_donor_region_variant, intron_variant
TBX6	XR_007064904.1 linkuse as main transcript	n.241+6C>T	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
TBX6	ENST00000395224.7 linkuse as main transcript	c.118+6C>T	splice_donor_region_variant, intron_variant	1	NM_004608.4	P1	O95947-1
TBX6	ENST00000279386.6 linkuse as main transcript	c.118+6C>T	splice_donor_region_variant, intron_variant	1		P1	O95947-1
TBX6	ENST00000553607.1 linkuse as main transcript	c.118+6C>T	splice_donor_region_variant, intron_variant	1			O95947-2
TBX6	ENST00000567664.5 linkuse as main transcript	c.118+6C>T	splice_donor_region_variant, intron_variant, NMD_transcript_variant	5			O95947-2

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3453

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00523

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0153

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0509

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0348

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0225

AC:

4368

AN:

194372

Hom.:

AF XY:

0.0219

AC XY:

2295

AN XY:

104810

show subpopulations

Gnomad AFR exome

AF:

0.00586

Gnomad AMR exome

AF:

0.00879

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.0465

Gnomad NFE exome

AF:

0.0362

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0294

AC:

42040

AN:

1432330

Hom.:

735

Cov.:

AF XY:

0.0285

AC XY:

20236

AN XY:

709820

show subpopulations

Gnomad4 AFR exome

AF:

0.00437

Gnomad4 AMR exome

AF:

0.00945

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.0441

Gnomad4 NFE exome

AF:

0.0341

Gnomad4 OTH exome

AF:

0.0230

GnomAD4 genome

AF:

0.0227

AC:

3456

AN:

152296

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1715

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00522

Gnomad4 AMR

AF:

0.0153

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0509

Gnomad4 NFE

AF:

0.0348

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0289

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00034

dbscSNV1_RF

Benign

0.0080

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