rs12544197

Variant names:

• chr8-109095596-G-A
• rs12544197
• NM_003301.7:c.789+7295G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-109095596-G-A
• chr8-109095596-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003301.7(TRHR):​c.789+7295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,772 control chromosomes in the GnomAD database, including 19,483 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 0.51 (19483 hom., cov: 31)
• Consequence: TRHR NM_003301.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 6 publications found

Genes affected

TRHR (HGNC:12299): (thyrotropin releasing hormone receptor) This gene encodes a G protein-coupled receptor for thyrotropin-releasing hormone (TRH). Upon binding to TRH, this receptor activates the inositol phospholipid-calcium-protein kinase C transduction pathway. Mutations in this gene have been associated with generalized thyrotropin-releasing hormone resistance. [provided by RefSeq, Sep 2011]

TRHR Gene-Disease associations (from GenCC):

• hypothyroidism, congenital, nongoitrous, 7

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• resistance to thyrotropin-releasing hormone syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 (AMR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRHR	NM_003301.7	c.789+7295G>A		intron_variant	Intron 2 of 2	ENST00000518632.2	NP_003292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRHR	ENST00000518632.2	c.789+7295G>A		intron_variant	Intron 2 of 2	5	NM_003301.7	ENSP00000430711.2
TRHR	ENST00000311762.2	c.789+7295G>A		intron_variant	Intron 1 of 1	1		ENSP00000309818.2

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76690 AN: 151654 Hom.: 19458 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.506 AC: 76763 AN: 151772 Hom.: 19483 Cov.: 31 AF XY: 0.509 AC XY: 37739 AN XY: 74156

African (AFR) AF: 0.518 AC: 21403 AN: 41328

American (AMR) AF: 0.591 AC: 9019 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1274 AN: 3464

East Asian (EAS) AF: 0.510 AC: 2627 AN: 5148

South Asian (SAS) AF: 0.530 AC: 2546 AN: 4804

European-Finnish (FIN) AF: 0.500 AC: 5268 AN: 10532

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32877 AN: 67918

Other (OTH) AF: 0.512 AC: 1081 AN: 2112

Alfa AF: 0.490 Hom.: 13629

Bravo AF: 0.513

Asia WGS AF: 0.541 AC: 1882 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	3.0
DANN	Benign	0.69
PhyloP100		0.082
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: rs12544197; hg19: chr8-110107825;