chr12-114364333-A-G

Position:

• chr12-114364333-A-G

Variant summary

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

The NM_181486.4(TBX5):​c.982+1832T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,046 control chromosomes in the GnomAD database, including 38,256 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 0.71 (38256 hom., cov: 31)
• Consequence: TBX5 NM_181486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

Genes affected

TBX5 (HGNC:11604): (T-box transcription factor 5) 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. This gene is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12. The encoded protein may play a role in heart development and specification of limb identity. Mutations in this gene have been associated with Holt-Oram syndrome, a developmental disorder affecting the heart and upper limbs. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBX5	NM_181486.4	c.982+1832T>C		intron_variant		ENST00000405440.7	NP_852259.1
TBX5	NM_000192.3	c.982+1832T>C		intron_variant			NP_000183.2
TBX5	NM_080717.4	c.832+1832T>C		intron_variant			NP_542448.1
TBX5	XM_017019912.2	c.1030+1832T>C		intron_variant			XP_016875401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBX5	ENST00000405440.7	c.982+1832T>C		intron_variant		1	NM_181486.4	ENSP00000384152.3
TBX5	ENST00000310346.8	c.982+1832T>C		intron_variant		1		ENSP00000309913.4
TBX5	ENST00000349716.9	c.832+1832T>C		intron_variant		1		ENSP00000337723.5

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107155 AN: 151928 Hom.: 38225 Cov.: 31

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.705 AC: 107229 AN: 152046 Hom.: 38256 Cov.: 31 AF XY: 0.700 AC XY: 52048 AN XY: 74322

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.681

Alfa AF: 0.710 Hom.: 4731

Bravo AF: 0.694

Asia WGS AF: 0.628 AC: 2185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.47

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: rs1895585; hg19: chr12-114802138;