1-118961220-C-G

Variant names:

• chr1-118961220-C-G
• rs984222
• NM_001330677.2:c.205+26371G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 72 publications found

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 Gene-Disease associations (from GenCC):

• pelviscapular dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBX15	NM_001330677.2	c.205+26371G>C		intron_variant	Intron 1 of 7	ENST00000369429.5	NP_001317606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX15	ENST00000369429.5	c.205+26371G>C		intron_variant	Intron 1 of 7	5	NM_001330677.2	ENSP00000358437.3
TBX15	ENST00000207157.7	c.-114+28135G>C		intron_variant	Intron 1 of 7	1		ENSP00000207157.3

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

African (AFR) AF: 0.437 AC: 18108 AN: 41422

American (AMR) AF: 0.586 AC: 8955 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1466 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2968 AN: 5174

South Asian (SAS) AF: 0.466 AC: 2243 AN: 4814

European-Finnish (FIN) AF: 0.741 AC: 7825 AN: 10562

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41681 AN: 67974

Other (OTH) AF: 0.535 AC: 1129 AN: 2110

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
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs984222; hg19: chr1-119503843;