Variant 3-46883225-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_000316.3(PTH1R):c.-48-287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 220,790 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.016 ( 38 hom., cov: 31)

Exomes 𝑓: 0.012 ( 8 hom. )

Consequence

PTH1R
NM_000316.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0380

Variant links:

Genes affected

PTH1R (HGNC:9608): (parathyroid hormone 1 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor family 2. This protein is a receptor for parathyroid hormone (PTH) and for parathyroid hormone-like hormone (PTHLH). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system. Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC), chondrodysplasia Blomstrand type (BOCD), as well as enchodromatosis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

PTH1R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 3-46883225-C-T is Benign according to our data. Variant chr3-46883225-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1188140.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2467/151468) while in subpopulation NFE AF= 0.023 (1557/67670). AF 95% confidence interval is 0.0221. There are 38 homozygotes in gnomad4. There are 1199 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTH1R	NM_000316.3 linkuse as main transcript	c.-48-287C>T		intron_variant		ENST00000449590.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
PTH1R	ENST00000449590.6 linkuse as main transcript	c.-48-287C>T	intron_variant	1	NM_000316.3	P1
PTH1R	ENST00000430002.6 linkuse as main transcript	c.-48-287C>T	intron_variant	1		P1
PTH1R	ENST00000418619.5 linkuse as main transcript	c.-48-287C>T	intron_variant	5		P1
PTH1R	ENST00000427125.6 linkuse as main transcript	c.-48-287C>T	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2469

AN:

151362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00407

Gnomad AMI

AF:

0.0419

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0230

Gnomad OTH

AF:

0.0178

GnomAD4 exome

AF:

0.0125

AC:

864

AN:

69322

Hom.:

AF XY:

0.0123

AC XY:

439

AN XY:

35616

show subpopulations

Gnomad4 AFR exome

AF:

0.000486

Gnomad4 AMR exome

AF:

0.00621

Gnomad4 ASJ exome

AF:

0.00395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00156

Gnomad4 FIN exome

AF:

0.0186

Gnomad4 NFE exome

AF:

0.0144

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.0163

AC:

2467

AN:

151468

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1199

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.00406

Gnomad4 AMR

AF:

0.0155

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.0345

Gnomad4 NFE

AF:

0.0230

Gnomad4 OTH

AF:

0.0176

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0149

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over