rs1990330

Positions:

• chr12-3038296-A-C
• chr12-3038296-A-G
• chr12-3038296-A-T

Variant summary

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

The ENST00000359864.8(TEAD4):​c.1038+188A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,132 control chromosomes in the GnomAD database, including 32,653 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 0.61 (32653 hom., cov: 33)
• Consequence: TEAD4 ENST00000359864.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

Genes affected

TEAD4 (HGNC:11717): (TEA domain transcription factor 4) This gene product is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which contain the TEA/ATTS DNA-binding domain. It is preferentially expressed in the skeletal muscle, and binds to the M-CAT regulatory element found in promoters of muscle-specific genes to direct their gene expression. Alternatively spliced transcripts encoding distinct isoforms, some of which are translated through the use of a non-AUG (UUG) initiation codon, 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEAD4	NM_003213.4	c.1038+188A>C		intron_variant		ENST00000359864.8	NP_003204.2
TEAD4	NM_201441.3	c.909+188A>C		intron_variant			NP_958849.1
TEAD4	NM_201443.3	c.651+188A>C		intron_variant			NP_958851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEAD4	ENST00000359864.8	c.1038+188A>C		intron_variant		1	NM_003213.4	ENSP00000352926	P1
TEAD4	ENST00000358409.7	c.909+188A>C		intron_variant		1		ENSP00000351184
TEAD4	ENST00000397122.6	c.651+188A>C		intron_variant		1		ENSP00000380311

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92267 AN: 152014 Hom.: 32645 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.607 AC: 92302 AN: 152132 Hom.: 32653 Cov.: 33 AF XY: 0.609 AC XY: 45298 AN XY: 74372

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.652

Alfa AF: 0.540 Hom.: 2438

Bravo AF: 0.596

Asia WGS AF: 0.779 AC: 2707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.79

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: rs1990330; hg19: chr12-3147462;