rs11996666

Variant names:

• chr8-53978288-G-T
• rs11996666
• NM_006756.4:c.825+737C>A

Variant summary

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

The NM_006756.4(TCEA1):​c.825+737C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,088 control chromosomes in the GnomAD database, including 4,283 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 0.20 (4283 hom., cov: 32)
• Consequence: TCEA1 NM_006756.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 5 publications found

Genes affected

TCEA1 (HGNC:11612): (transcription elongation factor A1) Predicted to enable DNA binding activity; translation elongation factor activity; and zinc ion binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within erythrocyte differentiation and positive regulation of transcription, DNA-templated. Located in nucleolus and nucleoplasm. Part of transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

LYPLA1-TCEA1 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEA1	NM_006756.4	c.825+737C>A		intron_variant	Intron 8 of 9	ENST00000521604.7	NP_006747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEA1	ENST00000521604.7	c.825+737C>A		intron_variant	Intron 8 of 9	1	NM_006756.4	ENSP00000428426.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30028 AN: 151970 Hom.: 4271 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.198 AC: 30068 AN: 152088 Hom.: 4283 Cov.: 32 AF XY: 0.211 AC XY: 15701 AN XY: 74330

African (AFR) AF: 0.147 AC: 6098 AN: 41492

American (AMR) AF: 0.306 AC: 4673 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 748 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3811 AN: 5174

South Asian (SAS) AF: 0.465 AC: 2242 AN: 4822

European-Finnish (FIN) AF: 0.241 AC: 2547 AN: 10552

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9168 AN: 67978

Other (OTH) AF: 0.215 AC: 455 AN: 2112

Alfa AF: 0.147 Hom.: 1598

Bravo AF: 0.200

Asia WGS AF: 0.563 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.23
PhyloP100		-0.12
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: rs11996666; hg19: chr8-54890848;