rs2702967

Positions:

• chr8-133056503-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+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

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]

PTCSC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLA	NM_001045556.3	c.61+3597C>T		intron_variant		ENST00000338087.10	NP_001039021.1
TG	NM_003235.5	c.7239+26480G>A		intron_variant		ENST00000220616.9	NP_003226.4
PTCSC1	NR_146773.1	n.1545G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TG	ENST00000220616.9	c.7239+26480G>A		intron_variant		1	NM_003235.5	ENSP00000220616	P1
SLA	ENST00000338087.10	c.61+3597C>T		intron_variant		1	NM_001045556.3	ENSP00000337548	P1
PTCSC1	ENST00000664551.1	n.1545G>A		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.465

Alfa AF: 0.483 Hom.: 5631

Bravo AF: 0.461

Asia WGS AF: 0.396 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.59

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: rs2702967; hg19: chr8-134068748;