8-133051907-C-T

Variant names:

• chr8-133051907-C-T
• rs1533910
• NM_003235.5:c.7239+21884C>T

Variant summary

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

The NM_003235.5(TG):​c.7239+21884C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,142 control chromosomes in the GnomAD database, including 3,596 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 0.21 (3596 hom., cov: 32)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 4 publications found

Genes affected

TG (HGNC:11764): (thyroglobulin) Thyroglobulin (Tg) is a glycoprotein homodimer produced predominantly by the thryroid gland. It acts as a substrate for the synthesis of thyroxine and triiodothyronine as well as the storage of the inactive forms of thyroid hormone and iodine. Thyroglobulin is secreted from the endoplasmic reticulum to its site of iodination, and subsequent thyroxine biosynthesis, in the follicular lumen. Mutations in this gene cause thyroid dyshormonogenesis, manifested as goiter, and are associated with moderate to severe congenital hypothyroidism. Polymorphisms in this gene are associated with susceptibility to autoimmune thyroid diseases (AITD) such as Graves disease and Hashimoto thryoiditis. [provided by RefSeq, Nov 2009]

SLA (HGNC:10902): (Src like adaptor) Predicted to enable signaling receptor binding activity. Predicted to be involved in cell differentiation; innate immune response; and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be located in cytosol. Predicted to be active in dendritic spine and focal adhesion. Predicted to be extrinsic component of cytoplasmic side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003235.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TG	NM_003235.5	MANE Select	c.7239+21884C>T		intron	N/A	NP_003226.4
	SLA	NM_001045556.3	MANE Select	c.62-992G>A		intron	N/A	NP_001039021.1
	SLA	NM_006748.4		c.182-992G>A		intron	N/A	NP_006739.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TG	ENST00000220616.9	TSL:1 MANE Select	c.7239+21884C>T		intron	N/A	ENSP00000220616.4
	SLA	ENST00000338087.10	TSL:1 MANE Select	c.62-992G>A		intron	N/A	ENSP00000337548.5
	SLA	ENST00000427060.6	TSL:1	c.182-992G>A		intron	N/A	ENSP00000394049.2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32350 AN: 152024 Hom.: 3595 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.213 AC: 32379 AN: 152142 Hom.: 3596 Cov.: 32 AF XY: 0.209 AC XY: 15534 AN XY: 74382

African (AFR) AF: 0.252 AC: 10438 AN: 41484

American (AMR) AF: 0.234 AC: 3570 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3472

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5174

South Asian (SAS) AF: 0.131 AC: 629 AN: 4818

European-Finnish (FIN) AF: 0.146 AC: 1548 AN: 10588

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14687 AN: 68002

Other (OTH) AF: 0.211 AC: 445 AN: 2114

Alfa AF: 0.208 Hom.: 6441

Bravo AF: 0.217

Asia WGS AF: 0.0860 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.64
PhyloP100		-1.4
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: rs1533910; hg19: chr8-134064152;