Genetic Variant PHGR1:p.Pro45Pro (chr15-40356189-A-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001145643.2(PHGR1):c.135A>T(p.Pro45Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,224,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000042 ( 0 hom., cov: 17)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PHGR1
NM_001145643.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.52

Publications

0 publications found

Variant links:

Genes affected

PHGR1 (HGNC:37226): (proline, histidine and glycine rich 1)

PHGR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 15-40356189-A-T is Benign according to our data. Variant chr15-40356189-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2645167.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.52 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHGR1	NM_001145643.2 link	c.135A>T	p.Pro45Pro	synonymous_variant	Exon 4 of 4	ENST00000448599.2	NP_001139115.1	C9JFL3A0A1L2EC20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHGR1	ENST00000448599.2 link	c.135A>T	p.Pro45Pro	synonymous_variant	Exon 4 of 4	5	NM_001145643.2	ENSP00000410024.2		C9JFL3

Frequencies

GnomAD3 genomes

AF:

0.0000417

AC:

AN:

71944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000546

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000543

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000294

AC:

AN:

101976

AF XY:

0.0000178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000175

Gnomad NFE exome

AF:

0.0000275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000163

AC:

AN:

1224698

Hom.:

Cov.:

AF XY:

0.00000167

AC XY:

AN XY:

600306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24640

American (AMR)

AF:

0.00

AC:

AN:

25958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18494

East Asian (EAS)

AF:

0.00

AC:

AN:

24686

South Asian (SAS)

AF:

0.0000153

AC:

AN:

65370

European-Finnish (FIN)

AF:

0.0000280

AC:

AN:

35722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4560

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

977510

Other (OTH)

AF:

0.00

AC:

AN:

47758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000417

AC:

AN:

71950

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

34208

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

16962

American (AMR)

AF:

0.00

AC:

AN:

6300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1986

East Asian (EAS)

AF:

0.00

AC:

AN:

2810

South Asian (SAS)

AF:

0.000548

AC:

AN:

1824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

116

European-Non Finnish (NFE)

AF:

0.0000543

AC:

AN:

36822

Other (OTH)

AF:

0.00

AC:

AN:

942

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0225104), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PHGR1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.33

(source)

DANN

Benign

0.72

PhyloP100

-3.5

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over