1-118884636-G-A

Variant names:

• chr1-118884636-G-A
• rs17022673
• NM_001330677.2:c.*96C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.612
• Publications: 0 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 -20 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_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBX15	NM_001330677.2	c.*96C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000369429.5	NP_001317606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBX15	ENST00000369429.5	c.*96C>T		3_prime_UTR_variant	Exon 8 of 8	5	NM_001330677.2	ENSP00000358437.3
TBX15	ENST00000207157.7	c.*96C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000207157.3
TBX15	ENST00000449873.5	c.*96C>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000398625.1

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

African (AFR) AF: 0.0312 AC: 700 AN: 22464

American (AMR) AF: 0.00104 AC: 31 AN: 29908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20132

East Asian (EAS) AF: 0.00 AC: 0 AN: 34998

South Asian (SAS) AF: 0.000173 AC: 12 AN: 69474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45036

Middle Eastern (MID) AF: 0.00194 AC: 6 AN: 3090

European-Non Finnish (NFE) AF: 0.00000424 AC: 3 AN: 707460

Other (OTH) AF: 0.00153 AC: 65 AN: 42476

GnomAD4 genome AF: 0.00711 AC: 1059 AN: 149024 Hom.: 22 Cov.: 31 AF XY: 0.00720 AC XY: 522 AN XY: 72532

African (AFR) AF: 0.0251 AC: 1017 AN: 40494

American (AMR) AF: 0.00187 AC: 28 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5050

South Asian (SAS) AF: 0.00 AC: 0 AN: 4718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9594

Middle Eastern (MID) AF: 0.00709 AC: 2 AN: 282

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67474

Other (OTH) AF: 0.00485 AC: 10 AN: 2062

Alfa AF: 0.00245 Hom.: 5

Bravo AF: 0.00794

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 08, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.80
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism

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: rs17022673; hg19: chr1-119427259;