rs3825214

chr12-114357638-G-Achr12-114357638-G-T

Variant summary

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

The NM_181486.4(TBX5):c.983-1532C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,154 control chromosomes in the GnomAD database, including 45,415 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 0.77 (45415 hom., cov: 32)
• Consequence: TBX5 NM_181486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBX5	NM_181486.4	c.983-1532C>T		intron_variant		ENST00000405440.7
TBX5	NM_000192.3	c.983-1532C>T		intron_variant
TBX5	NM_080717.4	c.833-1532C>T		intron_variant
TBX5	XM_017019912.2	c.1031-1532C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX5	ENST00000405440.7	c.983-1532C>T		intron_variant		1	NM_181486.4	P1
TBX5	ENST00000310346.8	c.983-1532C>T		intron_variant		1		P1
TBX5	ENST00000349716.9	c.833-1532C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117074 AN: 152036 Hom.: 45389 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.770 AC: 117142 AN: 152154 Hom.: 45415 Cov.: 32 AF XY: 0.764 AC XY: 56834 AN XY: 74394

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.765

Alfa AF: 0.793 Hom.: 111675

Bravo AF: 0.762

Asia WGS AF: 0.651 AC: 2265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.011
Dann	Benign	0.28

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: rs3825214; hg19: chr12-114795443;