rs1946295

chr12-114364556-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+1609T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 151,980 control chromosomes in the GnomAD database, including 37,395 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 0.70 (37395 hom., cov: 31)
• Consequence: TBX5 NM_181486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619

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=-0.95).
• 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	UniProt
TBX5	NM_181486.4	c.982+1609T>C		intron_variant		ENST00000405440.7
TBX5	NM_000192.3	c.982+1609T>C		intron_variant
TBX5	NM_080717.4	c.832+1609T>C		intron_variant
TBX5	XM_017019912.2	c.1030+1609T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBX5	ENST00000405440.7	c.982+1609T>C		intron_variant		1	NM_181486.4	P1
TBX5	ENST00000310346.8	c.982+1609T>C		intron_variant		1		P1
TBX5	ENST00000349716.9	c.832+1609T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105905 AN: 151862 Hom.: 37371 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.556

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: 0.678

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

GnomAD4 genome AF: 0.697 AC: 105972 AN: 151980 Hom.: 37395 Cov.: 31 AF XY: 0.692 AC XY: 51439 AN XY: 74290

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.556

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: 0.676

Alfa AF: 0.716 Hom.: 17913

Bravo AF: 0.685

Asia WGS AF: 0.625 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.7
Dann	Benign	0.84

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: rs1946295; hg19: chr12-114802361;