rs844107

Variant names:

• chr3-24121530-T-C
• rs844107
• NM_001354712.2:c.*1354A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-24121530-T-C
• chr3-24121530-T-A
• chr3-24121530-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001354712.2(THRB):​c.*1354A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,424 control chromosomes in the GnomAD database, including 15,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15911 hom., cov: 32)
  • Exomes 𝑓: 0.38 (35 hom.)
• Consequence: THRB NM_001354712.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0360
• Publications: 13 publications found

Genes affected

THRB (HGNC:11799): (thyroid hormone receptor beta) The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Mutations in this gene are known to be a cause of generalized thyroid hormone resistance (GTHR), a syndrome characterized by goiter and high levels of circulating thyroid hormone (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Several alternatively spliced transcript variants encoding the same protein have been observed for this gene. [provided by RefSeq, Jul 2008]

THRB Gene-Disease associations (from GenCC):

• thyroid hormone resistance, generalized, autosomal dominant

  Inheritance: SD, AD Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• thyroid hormone resistance, generalized, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-24121530-T-C is Benign according to our data. Variant chr3-24121530-T-C is described in ClinVar as Benign. ClinVar VariationId is 344613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354712.2. 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
	THRB	NM_001354712.2	MANE Select	c.*1354A>G		3_prime_UTR	Exon 11 of 11	NP_001341641.1	P10828-1
	THRB	NM_000461.5		c.*1354A>G		3_prime_UTR	Exon 10 of 10	NP_000452.2
	THRB	NM_001128176.3		c.*1354A>G		3_prime_UTR	Exon 11 of 11	NP_001121648.1	P10828-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THRB	ENST00000646209.2	MANE Select	c.*1354A>G		3_prime_UTR	Exon 11 of 11	ENSP00000496686.2	P10828-1
	THRB	ENST00000356447.9	TSL:1	c.*1354A>G		3_prime_UTR	Exon 11 of 11	ENSP00000348827.4	P10828-1
	THRB	ENST00000396671.7	TSL:5	c.*1354A>G		3_prime_UTR	Exon 10 of 10	ENSP00000379904.2	P10828-1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68527 AN: 151860 Hom.: 15879 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.383 AC: 170 AN: 444 Hom.: 35 Cov.: 0 AF XY: 0.399 AC XY: 107 AN XY: 268

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.373 AC: 155 AN: 416

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.611 AC: 11 AN: 18

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.451 AC: 68618 AN: 151980 Hom.: 15911 Cov.: 32 AF XY: 0.454 AC XY: 33768 AN XY: 74322

African (AFR) AF: 0.551 AC: 22824 AN: 41428

American (AMR) AF: 0.464 AC: 7080 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1578 AN: 3468

East Asian (EAS) AF: 0.630 AC: 3256 AN: 5168

South Asian (SAS) AF: 0.454 AC: 2187 AN: 4822

European-Finnish (FIN) AF: 0.363 AC: 3841 AN: 10582

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26314 AN: 67948

Other (OTH) AF: 0.432 AC: 911 AN: 2110

Alfa AF: 0.409 Hom.: 22139

Bravo AF: 0.468

Asia WGS AF: 0.520 AC: 1805 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Thyroid hormone resistance, generalized, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		0.036
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: rs844107; hg19: chr3-24163021;