rs724448

Variant names:

• chr3-46894244-A-C
• rs724448
• NM_000316.3:c.178+235A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-46894244-A-C
• chr3-46894244-A-G
• chr3-46894244-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000316.3(PTH1R):​c.178+235A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,932 control chromosomes in the GnomAD database, including 20,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (20216 hom., cov: 31)
• Consequence: PTH1R NM_000316.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.768
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• metaphyseal chondrodysplasia, Jansen type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• primary failure of tooth eruption

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• chondrodysplasia Blomstrand type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• Eiken syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ENSG00000308167 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-46894244-A-C is Benign according to our data. Variant chr3-46894244-A-C is described in ClinVar as Benign. ClinVar VariationId is 1246255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000316.3. 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
	PTH1R	NM_000316.3	MANE Select	c.178+235A>C		intron	N/A	NP_000307.1	Q03431
	PTH1R	NM_001184744.1		c.178+235A>C		intron	N/A	NP_001171673.1	Q0VGD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTH1R	ENST00000449590.6	TSL:1 MANE Select	c.178+235A>C		intron	N/A	ENSP00000402723.1	Q03431
	PTH1R	ENST00000313049.9	TSL:1	c.178+235A>C		intron	N/A	ENSP00000321999.4	Q03431
	PTH1R	ENST00000430002.6	TSL:1	c.178+235A>C		intron	N/A	ENSP00000413774.2	Q03431

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75086 AN: 151814 Hom.: 20199 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.495 AC: 75139 AN: 151932 Hom.: 20216 Cov.: 31 AF XY: 0.493 AC XY: 36643 AN XY: 74258

African (AFR) AF: 0.273 AC: 11334 AN: 41444

American (AMR) AF: 0.529 AC: 8071 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1931 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2361 AN: 5150

South Asian (SAS) AF: 0.544 AC: 2617 AN: 4808

European-Finnish (FIN) AF: 0.622 AC: 6564 AN: 10560

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40623 AN: 67926

Other (OTH) AF: 0.505 AC: 1064 AN: 2106

Alfa AF: 0.530 Hom.: 7054

Bravo AF: 0.475

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.4
DANN	Benign	0.37
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs724448; hg19: chr3-46935734;