chr11-12676493-A-G

Variant names:

• chr11-12676493-A-G
• rs7926971
• NM_021961.6:c.-55+932A>G

Variant summary

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

The NM_021961.6(TEAD1):​c.-55+932A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,096 control chromosomes in the GnomAD database, including 13,230 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 0.41 (13230 hom., cov: 33)
• Consequence: TEAD1 NM_021961.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 35 publications found

Genes affected

TEAD1 (HGNC:11714): (TEA domain transcription factor 1) This gene encodes a ubiquitous transcriptional enhancer factor that is a member of the TEA/ATTS domain family. This protein directs the transactivation of a wide variety of genes and, in placental cells, also acts as a transcriptional repressor. Mutations in this gene cause Sveinsson's chorioretinal atrophy. Additional transcript variants have been described but their full-length natures have not been experimentally verified. [provided by RefSeq, May 2010]

TEAD1 Gene-Disease associations (from GenCC):

• helicoid peripapillary chorioretinal degeneration

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Aicardi syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021961.6. 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
	TEAD1	NM_021961.6	MANE Select	c.-55+932A>G		intron	N/A	NP_068780.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEAD1	ENST00000527636.7	TSL:1 MANE Select	c.-55+932A>G		intron	N/A	ENSP00000435233.2
	TEAD1	ENST00000334310.10	TSL:1	c.-100+932A>G		intron	N/A	ENSP00000334754.6
	TEAD1	ENST00000527575.6	TSL:5	c.-55+932A>G		intron	N/A	ENSP00000435977.2

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62512 AN: 151978 Hom.: 13213 Cov.: 33

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.411 AC: 62543 AN: 152096 Hom.: 13230 Cov.: 33 AF XY: 0.409 AC XY: 30413 AN XY: 74342

African (AFR) AF: 0.332 AC: 13787 AN: 41492

American (AMR) AF: 0.409 AC: 6263 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1294 AN: 3468

East Asian (EAS) AF: 0.315 AC: 1629 AN: 5164

South Asian (SAS) AF: 0.563 AC: 2713 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4547 AN: 10562

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31033 AN: 67976

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.434 Hom.: 38935

Bravo AF: 0.399

Asia WGS AF: 0.510 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-0.20
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: rs7926971; hg19: chr11-12698040;