dbSNP rs2292767: PRLHR:c.*3608G>A (chr10-118590524-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004248.3(PRLHR):c.*3608G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,124 control chromosomes in the GnomAD database, including 7,183 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 0.28 ( 7183 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

PRLHR
NM_004248.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.291

Publications

5 publications found

Variant links:

Genes affected

PRLHR (HGNC:4464): (prolactin releasing hormone receptor) Predicted to enable neuropeptide receptor activity. Predicted to be involved in female pregnancy. Predicted to act upstream of or within G protein-coupled receptor signaling pathway; feeding behavior; and hormone metabolic process. Located in cilium. Implicated in hypertension. [provided by Alliance of Genome Resources, Apr 2022]

PRLHR links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004248.3. 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
	PRLHR	NM_004248.3	MANE Select	c.*3608G>A		3_prime_UTR	Exon 2 of 2	NP_004239.2	P49683

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRLHR	ENST00000239032.4	TSL:1 MANE Select	c.*3608G>A		3_prime_UTR	Exon 2 of 2	ENSP00000239032.2	P49683

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42179

AN:

152004

Hom.:

7187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0902

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.277

AC:

42165

AN:

152122

Hom.:

7183

Cov.:

AF XY:

0.276

AC XY:

20525

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0899

AC:

3733

AN:

41516

American (AMR)

AF:

0.234

AC:

3579

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

935

AN:

3472

East Asian (EAS)

AF:

0.255

AC:

1319

AN:

5172

South Asian (SAS)

AF:

0.225

AC:

1086

AN:

4816

European-Finnish (FIN)

AF:

0.418

AC:

4412

AN:

10564

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26329

AN:

67970

Other (OTH)

AF:

0.257

AC:

543

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1451

2902

4352

5803

7254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.330

Hom.:

17767

Bravo

AF:

0.257

Asia WGS

AF:

0.226

AC:

786

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.29

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over