rs2702967

Variant names:

• chr8-133056503-G-A
• rs2702967
• NM_003235.5:c.7239+26480G>A

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+26480G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,952 control chromosomes in the GnomAD database, including 17,411 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 0.47 (17411 hom., cov: 31)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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]

PTCSC1 (HGNC:37127): (papillary thyroid carcinoma susceptibility candidate 1)

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 (NFE) allele frequency at 95% confidence interval = 0.494 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+26480G>A		intron	N/A	NP_003226.4
	SLA	NM_001045556.3	MANE Select	c.61+3597C>T		intron	N/A	NP_001039021.1
	SLA	NM_006748.4		c.181+3597C>T		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+26480G>A		intron	N/A	ENSP00000220616.4
	SLA	ENST00000338087.10	TSL:1 MANE Select	c.61+3597C>T		intron	N/A	ENSP00000337548.5
	SLA	ENST00000427060.6	TSL:1	c.181+3597C>T		intron	N/A	ENSP00000394049.2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72110 AN: 151834 Hom.: 17406 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.475 AC: 72139 AN: 151952 Hom.: 17411 Cov.: 31 AF XY: 0.474 AC XY: 35222 AN XY: 74264

African (AFR) AF: 0.459 AC: 19015 AN: 41424

American (AMR) AF: 0.369 AC: 5635 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2248 AN: 5138

South Asian (SAS) AF: 0.436 AC: 2098 AN: 4816

European-Finnish (FIN) AF: 0.574 AC: 6069 AN: 10564

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

European-Non Finnish (NFE) AF: 0.498 AC: 33845 AN: 67936

Other (OTH) AF: 0.465 AC: 981 AN: 2108

Alfa AF: 0.483 Hom.: 5720

Bravo AF: 0.461

Asia WGS AF: 0.396 AC: 1382 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	0.24
DANN	Benign	0.59
PhyloP100		-1.3
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: rs2702967; hg19: chr8-134068748;