rs5662

Variant names:

• chr3-129977111-T-C
• rs5662
• NM_007117.5:c.624T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-129977111-T-C
• chr3-129977111-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007117.5(TRH):​c.624T>C​(p.Leu208Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,559,382 control chromosomes in the GnomAD database, including 768,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70518 hom., cov: 30)
  • Exomes 𝑓: 1.0 (697929 hom.)
• Consequence: TRH NM_007117.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.03
• Publications: 11 publications found

Genes affected

TRH (HGNC:12298): (thyrotropin releasing hormone) This gene encodes a member of the thyrotropin-releasing hormone family. Cleavage of the encoded proprotein releases mature thyrotropin-releasing hormone, which is a tripeptide hypothalamic regulatory hormone. The human proprotein contains six thyrotropin-releasing hormone tripeptides. Thyrotropin-releasing hormone is involved in the regulation and release of thyroid-stimulating hormone, as well as prolactin. Deficiency of this hormone has been associated with hypothalamic hypothyroidism. [provided by RefSeq, May 2013]

LOC124906284 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-129977111-T-C is Benign according to our data. Variant chr3-129977111-T-C is described in ClinVar as Benign. ClinVar VariationId is 260116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007117.5. 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
	TRH	NM_007117.5	MANE Select	c.624T>C	p.Leu208Leu	synonymous	Exon 3 of 3	NP_009048.1	P20396

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRH	ENST00000302649.4	TSL:1 MANE Select	c.624T>C	p.Leu208Leu	synonymous	Exon 3 of 3	ENSP00000303452.3	P20396
	TRH	ENST00000507066.1	TSL:5	c.612T>C	p.Leu204Leu	synonymous	Exon 3 of 3	ENSP00000426522.1	D6RFM1
	ENSG00000250643	ENST00000785099.1		n.298-5003A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146087 AN: 151932 Hom.: 70477 Cov.: 30

Gnomad AFR AF: 0.870

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.962

GnomAD2 exomes AF: 0.988 AC: 207976 AN: 210400 AF XY: 0.991

Gnomad AFR exome AF: 0.862

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.993

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.996 AC: 1401244 AN: 1407332 Hom.: 697929 Cov.: 82 AF XY: 0.996 AC XY: 692487 AN XY: 695202

African (AFR) AF: 0.856 AC: 26503 AN: 30976

American (AMR) AF: 0.990 AC: 34003 AN: 34334

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 22590 AN: 22734

East Asian (EAS) AF: 1.00 AC: 39164 AN: 39164

South Asian (SAS) AF: 1.00 AC: 77964 AN: 77994

European-Finnish (FIN) AF: 1.00 AC: 51518 AN: 51518

Middle Eastern (MID) AF: 0.992 AC: 5329 AN: 5374

European-Non Finnish (NFE) AF: 1.00 AC: 1087063 AN: 1087502

Other (OTH) AF: 0.989 AC: 57110 AN: 57736

GnomAD4 genome AF: 0.961 AC: 146187 AN: 152050 Hom.: 70518 Cov.: 30 AF XY: 0.963 AC XY: 71576 AN XY: 74298

African (AFR) AF: 0.870 AC: 36067 AN: 41468

American (AMR) AF: 0.981 AC: 15013 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3443 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5051 AN: 5052

South Asian (SAS) AF: 1.00 AC: 4823 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10624

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67929 AN: 67982

Other (OTH) AF: 0.962 AC: 2034 AN: 2114

Alfa AF: 0.987 Hom.: 167610

Bravo AF: 0.955

Asia WGS AF: 0.990 AC: 3441 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Hypothalamic hypothyroidism (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.44
PhyloP100		-1.0
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: rs5662; hg19: chr3-129695954; COSMIC: COSV108137482;