rs10500766

Variant names:

• chr11-12898362-A-G
• rs10500766
• NM_021961.6:c.700-3578A>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.700-3578A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 151,626 control chromosomes in the GnomAD database, including 1,053 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 0.085 (1053 hom., cov: 31)
• Consequence: TEAD1 NM_021961.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEAD1	NM_021961.6	c.700-3578A>G		intron_variant	Intron 9 of 12	ENST00000527636.7	NP_068780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEAD1	ENST00000527636.7	c.700-3578A>G		intron_variant	Intron 9 of 12	1	NM_021961.6	ENSP00000435233.2
TEAD1	ENST00000334310.10	c.666+15237A>G		intron_variant	Intron 9 of 11	1		ENSP00000334754.6
TEAD1	ENST00000526600.1	c.412-3578A>G		intron_variant	Intron 4 of 7	1		ENSP00000435393.1
TEAD1	ENST00000527575.6	c.699+15237A>G		intron_variant	Intron 8 of 10	5		ENSP00000435977.2

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12877 AN: 151522 Hom.: 1054 Cov.: 31

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.0367

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0748

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

GnomAD4 genome AF: 0.0850 AC: 12890 AN: 151626 Hom.: 1053 Cov.: 31 AF XY: 0.0916 AC XY: 6778 AN XY: 74024

African (AFR) AF: 0.0699 AC: 2891 AN: 41342

American (AMR) AF: 0.0798 AC: 1218 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0367 AC: 127 AN: 3462

East Asian (EAS) AF: 0.458 AC: 2350 AN: 5130

South Asian (SAS) AF: 0.0420 AC: 202 AN: 4804

European-Finnish (FIN) AF: 0.191 AC: 1993 AN: 10412

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0576 AC: 3915 AN: 67914

Other (OTH) AF: 0.0760 AC: 160 AN: 2104

Alfa AF: 0.0585 Hom.: 170

Bravo AF: 0.0830

Asia WGS AF: 0.197 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.60
PhyloP100		-0.98
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: rs10500766; hg19: chr11-12919909;