rs2252696

Variant names:

• chr8-133051287-C-A
• rs2252696
• NM_003235.5:c.7239+21264C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-133051287-C-A
• chr8-133051287-C-G

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+21264C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,982 control chromosomes in the GnomAD database, including 19,348 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 0.50 (19348 hom., cov: 31)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TG	NM_003235.5	c.7239+21264C>A		intron_variant	Intron 41 of 47	ENST00000220616.9	NP_003226.4
SLA	NM_001045556.3	c.62-372G>T		intron_variant	Intron 3 of 8	ENST00000338087.10	NP_001039021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9	c.7239+21264C>A		intron_variant	Intron 41 of 47	1	NM_003235.5	ENSP00000220616.4
SLA	ENST00000338087.10	c.62-372G>T		intron_variant	Intron 3 of 8	1	NM_001045556.3	ENSP00000337548.5

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75806 AN: 151864 Hom.: 19326 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.499 AC: 75873 AN: 151982 Hom.: 19348 Cov.: 31 AF XY: 0.495 AC XY: 36800 AN XY: 74300

African (AFR) AF: 0.519 AC: 21473 AN: 41412

American (AMR) AF: 0.434 AC: 6625 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3464

East Asian (EAS) AF: 0.209 AC: 1080 AN: 5164

South Asian (SAS) AF: 0.390 AC: 1881 AN: 4826

European-Finnish (FIN) AF: 0.510 AC: 5397 AN: 10572

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36025 AN: 67960

Other (OTH) AF: 0.476 AC: 1004 AN: 2110

Alfa AF: 0.505 Hom.: 36031

Bravo AF: 0.491

Asia WGS AF: 0.300 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.80
PhyloP100		-0.46
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: rs2252696; hg19: chr8-134063532;