rs4656579

chr1-168304963-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005149.3(TBX19):c.728-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,592,222 control chromosomes in the GnomAD database, including 357,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28832 hom., cov: 32)
  • Exomes 𝑓: 0.67 (329058 hom.)
• Consequence: TBX19 NM_005149.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.642

Genes affected

TBX19 (HGNC:11596): (T-box transcription factor 19) 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. Mutations in this gene were found in patients with isolated deficiency of pituitary POMC-derived ACTH, suggesting an essential role for this gene in differentiation of the pituitary POMC lineage. ACTH deficiency is characterized by adrenal insufficiency symptoms such as weight loss, lack of appetite (anorexia), weakness, nausea, vomiting, and low blood pressure. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-168304963-G-A is Benign according to our data. Variant chr1-168304963-G-A is described in ClinVar as [Benign]. Clinvar id is 1334932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX19	NM_005149.3	c.728-45G>A		intron_variant		ENST00000367821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX19	ENST00000367821.8	c.728-45G>A		intron_variant		1	NM_005149.3	P1
TBX19	ENST00000431969.5	c.525-3779G>A		intron_variant		5
TBX19	ENST00000441464.1	c.225-45G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91957 AN: 151944 Hom.: 28810 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.606

GnomAD3 exomes AF: 0.603 AC: 148695 AN: 246620 Hom.: 46733 AF XY: 0.602 AC XY: 80637 AN XY: 133844

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.583

Gnomad ASJ exome AF: 0.665

Gnomad EAS exome AF: 0.340

Gnomad SAS exome AF: 0.445

Gnomad FIN exome AF: 0.614

Gnomad NFE exome AF: 0.705

Gnomad OTH exome AF: 0.629

GnomAD4 exome AF: 0.669 AC: 963900 AN: 1440160 Hom.: 329058 Cov.: 27 AF XY: 0.664 AC XY: 476576 AN XY: 717862

Gnomad4 AFR exome AF: 0.482

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.663

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.711

Gnomad4 OTH exome AF: 0.638

GnomAD4 genome AF: 0.605 AC: 92022 AN: 152062 Hom.: 28832 Cov.: 32 AF XY: 0.594 AC XY: 44118 AN XY: 74332

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.609

Alfa AF: 0.681 Hom.: 53547

Bravo AF: 0.601

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital isolated adrenocorticotropic hormone deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.1
Dann	Benign	0.36

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

Other links and lift over

dbSNP: rs4656579; hg19: chr1-168274201; COSMIC: COSV63198712; COSMIC: COSV63198712;