rs12289262

Variant names:

• chr11-12873211-C-T
• rs12289262
• NM_021961.6:c.331-6497C>T

Variant summary

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

The NM_021961.6(TEAD1):​c.331-6497C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,170 control chromosomes in the GnomAD database, including 4,170 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 0.23 (4170 hom., cov: 33)
• Consequence: TEAD1 NM_021961.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEAD1	NM_021961.6	c.331-6497C>T		intron_variant	Intron 5 of 12	ENST00000527636.7	NP_068780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEAD1	ENST00000527636.7	c.331-6497C>T		intron_variant	Intron 5 of 12	1	NM_021961.6	ENSP00000435233.2
TEAD1	ENST00000334310.10	c.286-5678C>T		intron_variant	Intron 4 of 11	1		ENSP00000334754.6
TEAD1	ENST00000527575.6	c.331-6497C>T		intron_variant	Intron 4 of 10	5		ENSP00000435977.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34437 AN: 152052 Hom.: 4168 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.226 AC: 34457 AN: 152170 Hom.: 4170 Cov.: 33 AF XY: 0.225 AC XY: 16755 AN XY: 74402

African (AFR) AF: 0.169 AC: 7029 AN: 41530

American (AMR) AF: 0.205 AC: 3139 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1250 AN: 5170

South Asian (SAS) AF: 0.387 AC: 1868 AN: 4826

European-Finnish (FIN) AF: 0.193 AC: 2046 AN: 10588

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17482 AN: 67982

Other (OTH) AF: 0.255 AC: 540 AN: 2114

Alfa AF: 0.252 Hom.: 7939

Bravo AF: 0.222

Asia WGS AF: 0.362 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.50
PhyloP100		0.17
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: rs12289262; hg19: chr11-12894758;