rs4736618

Positions:

• chr8-133048214-T-C

Variant summary

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

The ENST00000220616.9(TG):​c.7239+18191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,110 control chromosomes in the GnomAD database, including 1,392 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 0.13 (1392 hom., cov: 32)
• Consequence: TG ENST00000220616.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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 (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLA	NM_001045556.3	c.249-281A>G		intron_variant		ENST00000338087.10	NP_001039021.1
TG	NM_003235.5	c.7239+18191T>C		intron_variant		ENST00000220616.9	NP_003226.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9	c.7239+18191T>C		intron_variant		1	NM_003235.5	ENSP00000220616	P1
SLA	ENST00000338087.10	c.249-281A>G		intron_variant		1	NM_001045556.3	ENSP00000337548	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19831 AN: 151992 Hom.: 1397 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.130 AC: 19825 AN: 152110 Hom.: 1392 Cov.: 32 AF XY: 0.127 AC XY: 9432 AN XY: 74364

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.0733

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.131

Alfa AF: 0.136 Hom.: 1933

Bravo AF: 0.135

Asia WGS AF: 0.0340 AC: 117 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	1.3
DANN	Benign	0.50

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: rs4736618; hg19: chr8-134060459;