NM_005048.4:c.178+3915G>T

Variant names:

• chr2-208432218-G-T
• rs10497900
• NM_005048.4:c.178+3915G>T

Variant summary

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

The NM_005048.4(PTH2R):​c.178+3915G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,124 control chromosomes in the GnomAD database, including 10,876 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 0.35 (10876 hom., cov: 33)
• Consequence: PTH2R NM_005048.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 5 publications found

Genes affected

PTH2R (HGNC:9609): (parathyroid hormone 2 receptor) The protein encoded by this gene is a member of the G-protein coupled receptor 2 family. This protein is a receptor for parathyroid hormone (PTH). This receptor is more selective in ligand recognition and has a more specific tissue distribution compared to parathyroid hormone receptor 1 (PTHR1). It is activated only by PTH and not by parathyroid hormone-like hormone (PTHLH) and is particularly abundant in brain and pancreas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005048.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTH2R	NM_005048.4	MANE Select	c.178+3915G>T		intron	N/A	NP_005039.1
	PTH2R	NM_001309516.2		c.-156+3915G>T		intron	N/A	NP_001296445.1
	PTH2R	NM_001371905.1		c.-156+3915G>T		intron	N/A	NP_001358834.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTH2R	ENST00000272847.7	TSL:1 MANE Select	c.178+3915G>T		intron	N/A	ENSP00000272847.2
	PTH2R	ENST00000617735.4	TSL:2	c.-156+3915G>T		intron	N/A	ENSP00000482485.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52638 AN: 152006 Hom.: 10872 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.346 AC: 52643 AN: 152124 Hom.: 10876 Cov.: 33 AF XY: 0.353 AC XY: 26266 AN XY: 74366

African (AFR) AF: 0.111 AC: 4591 AN: 41532

American (AMR) AF: 0.446 AC: 6826 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2094 AN: 5162

South Asian (SAS) AF: 0.335 AC: 1617 AN: 4824

European-Finnish (FIN) AF: 0.537 AC: 5670 AN: 10566

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29156 AN: 67960

Other (OTH) AF: 0.377 AC: 797 AN: 2112

Alfa AF: 0.396 Hom.: 16650

Bravo AF: 0.330

Asia WGS AF: 0.380 AC: 1319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.11
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: rs10497900; hg19: chr2-209296943;