rs2253035

chr8-133048815-G-Cchr8-133048815-G-T

Variant summary

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

The NM_003235.5(TG):c.7239+18792G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 169,634 control chromosomes in the GnomAD database, including 5,540 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 0.25 (4844 hom., cov: 32)
  • Exomes 𝑓: 0.26 (696 hom.)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLA	NM_001045556.3	c.249-882C>G		intron_variant		ENST00000338087.10
TG	NM_003235.5	c.7239+18792G>C		intron_variant		ENST00000220616.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TG	ENST00000220616.9	c.7239+18792G>C		intron_variant		1	NM_003235.5	P1
SLA	ENST00000338087.10	c.249-882C>G		intron_variant		1	NM_001045556.3	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37356 AN: 152026 Hom.: 4849 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.258 AC: 4520 AN: 17490 Hom.: 696 Cov.: 0 AF XY: 0.253 AC XY: 2374 AN XY: 9376

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.246 AC: 37365 AN: 152144 Hom.: 4844 Cov.: 32 AF XY: 0.241 AC XY: 17888 AN XY: 74348

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.250

Alfa AF: 0.264 Hom.: 678

Bravo AF: 0.241

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.13
Dann	Benign	0.42

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: rs2253035; hg19: chr8-134061060;