1-118884636-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.612

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 -14 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_single_submitter, 1 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 GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX15	NM_001330677.2	c.*96C>T		3_prime_UTR_variant	8/8	ENST00000369429.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX15	ENST00000369429.5	c.*96C>T		3_prime_UTR_variant	8/8	5	NM_001330677.2	P1
TBX15	ENST00000207157.7	c.*96C>T		3_prime_UTR_variant	8/8	1
TBX15	ENST00000449873.5	c.*96C>T		3_prime_UTR_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.00712 AC: 1061 AN: 148974 Hom.: 22 Cov.: 31

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.: 13 Cov.: 19 AF XY: 0.000680 AC XY: 339 AN XY: 498654

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.: 22 Cov.: 31 AF XY: 0.00720 AC XY: 522 AN XY: 72532

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.: 1

Bravo AF: 0.00794

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 08, 2019

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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

Other links and lift over

dbSNP: rs17022673; hg19: chr1-119427259;