rs1990330

Variant names:

• chr12-3038296-A-C
• rs1990330
• NM_003213.4:c.1038+188A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003213.4(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 NM_003213.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003213.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEAD4	NM_003213.4	MANE Select	c.1038+188A>C		intron	N/A	NP_003204.2
	TEAD4	NM_201441.3		c.909+188A>C		intron	N/A	NP_958849.1
	TEAD4	NM_201443.3		c.651+188A>C		intron	N/A	NP_958851.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEAD4	ENST00000359864.8	TSL:1 MANE Select	c.1038+188A>C		intron	N/A	ENSP00000352926.3
	TEAD4	ENST00000358409.7	TSL:1	c.909+188A>C		intron	N/A	ENSP00000351184.3
	TEAD4	ENST00000397122.6	TSL:1	c.651+188A>C		intron	N/A	ENSP00000380311.2

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

African (AFR) AF: 0.218 AC: 9028 AN: 41498

American (AMR) AF: 0.741 AC: 11331 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2503 AN: 3472

East Asian (EAS) AF: 0.942 AC: 4861 AN: 5160

South Asian (SAS) AF: 0.776 AC: 3740 AN: 4822

European-Finnish (FIN) AF: 0.685 AC: 7253 AN: 10588

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51386 AN: 67980

Other (OTH) AF: 0.652 AC: 1378 AN: 2112

Alfa AF: 0.522 Hom.: 2463

Bravo AF: 0.596

Asia WGS AF: 0.779 AC: 2707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.3
DANN	Benign	0.79
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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: rs1990330; hg19: chr12-3147462; COSMIC: COSV108188766; COSMIC: COSV108188766;