rs2739136

Variant names:

• chr8-133056947-G-A
• rs2739136
• NM_003235.5:c.7239+26924G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-133056947-G-A
• chr8-133056947-G-T

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+26924G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,048 control chromosomes in the GnomAD database, including 43,771 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 0.75 (43771 hom., cov: 31)
• Consequence: TG NM_003235.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TG	NM_003235.5	c.7239+26924G>A		intron_variant	Intron 41 of 47	ENST00000220616.9	NP_003226.4
SLA	NM_001045556.3	c.61+3153C>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+26924G>A		intron_variant	Intron 41 of 47	1	NM_003235.5	ENSP00000220616.4
SLA	ENST00000338087.10	c.61+3153C>T		intron_variant	Intron 3 of 8	1	NM_001045556.3	ENSP00000337548.5

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113997 AN: 151930 Hom.: 43719 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.750 AC: 114096 AN: 152048 Hom.: 43771 Cov.: 31 AF XY: 0.743 AC XY: 55206 AN XY: 74312

African (AFR) AF: 0.889 AC: 36914 AN: 41506

American (AMR) AF: 0.629 AC: 9619 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2558 AN: 3470

East Asian (EAS) AF: 0.441 AC: 2263 AN: 5132

South Asian (SAS) AF: 0.578 AC: 2783 AN: 4818

European-Finnish (FIN) AF: 0.726 AC: 7660 AN: 10554

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49937 AN: 67968

Other (OTH) AF: 0.717 AC: 1511 AN: 2108

Alfa AF: 0.753 Hom.: 5393

Bravo AF: 0.747

Asia WGS AF: 0.515 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-0.16
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: rs2739136; hg19: chr8-134069192;