rs528310955

Variant names:

• chr15-40356189-A-C
• rs528310955
• NM_001145643.2:c.135A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-40356189-A-C
• chr15-40356189-A-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001145643.2(PHGR1):​c.135A>C​(p.Pro45Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P45P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000083 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHGR1 NM_001145643.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52
• Publications: 0 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• 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	c.135A>C	p.Pro45Pro	synonymous_variant	Exon 4 of 4	ENST00000448599.2	NP_001139115.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000834 AC: 6 AN: 71932 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.0000591

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000543

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000543

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1224672 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 600290

African (AFR) AF: 0.00 AC: 0 AN: 24640

American (AMR) AF: 0.00 AC: 0 AN: 25958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18494

East Asian (EAS) AF: 0.00 AC: 0 AN: 24686

South Asian (SAS) AF: 0.00 AC: 0 AN: 65354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 977500

Other (OTH) AF: 0.00 AC: 0 AN: 47756

GnomAD4 genome AF: 0.0000834 AC: 6 AN: 71932 Hom.: 0 Cov.: 17 AF XY: 0.0000878 AC XY: 3 AN XY: 34184

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

African (AFR) AF: 0.0000591 AC: 1 AN: 16930

American (AMR) AF: 0.000159 AC: 1 AN: 6292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1986

East Asian (EAS) AF: 0.00 AC: 0 AN: 2822

South Asian (SAS) AF: 0.00 AC: 0 AN: 1832

European-Finnish (FIN) AF: 0.000543 AC: 2 AN: 3680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 124

European-Non Finnish (NFE) AF: 0.0000543 AC: 2 AN: 36830

Other (OTH) AF: 0.00 AC: 0 AN: 930

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.37
DANN	Benign	0.62
PhyloP100		-3.5

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: rs528310955; hg19: chr15-40648390;