rs2256366

chr8-133044857-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003235.5(TG):c.7239+14834G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 878,576 control chromosomes in the GnomAD database, including 17,877 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 0.15 (2510 hom., cov: 32)
  • Exomes 𝑓: 0.17 (15367 hom.)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLA	NM_001045556.3	c.484+127C>T		intron_variant		ENST00000338087.10
TG	NM_003235.5	c.7239+14834G>A		intron_variant		ENST00000220616.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9	c.7239+14834G>A		intron_variant		1	NM_003235.5	P1
SLA	ENST00000338087.10	c.484+127C>T		intron_variant		1	NM_001045556.3	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23201 AN: 152112 Hom.: 2502 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.174 AC: 126715 AN: 726346 Hom.: 15367 AF XY: 0.179 AC XY: 67408 AN XY: 376552

Gnomad4 AFR exome AF: 0.0745

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.508

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.152 AC: 23215 AN: 152230 Hom.: 2510 Cov.: 32 AF XY: 0.164 AC XY: 12190 AN XY: 74418

Gnomad4 AFR AF: 0.0759

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.173

Alfa AF: 0.145 Hom.: 487

Bravo AF: 0.156

Asia WGS AF: 0.405 AC: 1408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.24
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs2256366; hg19: chr8-134057102;