1-118961220-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330677.2(TBX15):c.205+26371G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,010 control chromosomes in the GnomAD database, including 24,613 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 0.56 (24613 hom., cov: 32)
• Consequence: TBX15 NM_001330677.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX15	NM_001330677.2	c.205+26371G>C		intron_variant		ENST00000369429.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX15	ENST00000369429.5	c.205+26371G>C		intron_variant		5	NM_001330677.2	P1
TBX15	ENST00000207157.7	c.-114+28135G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85095 AN: 151892 Hom.: 24613 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.741

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.560 AC: 85107 AN: 152010 Hom.: 24613 Cov.: 32 AF XY: 0.563 AC XY: 41831 AN XY: 74288

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.535

Alfa AF: 0.582 Hom.: 13376

Bravo AF: 0.543

Asia WGS AF: 0.494 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.085
Dann	Benign	0.37

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: rs984222; hg19: chr1-119503843;