rs180730

Variant names:

• chr4-120880635-G-A
• rs180730
• NM_018699.4:c.177+26839C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-120880635-G-A
• chr4-120880635-G-C
• chr4-120880635-G-T

Variant summary

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

The NM_018699.4(PRDM5):​c.177+26839C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,474 control chromosomes in the GnomAD database, including 5,146 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 0.25 (5146 hom., cov: 32)
• Consequence: PRDM5 NM_018699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 17 publications found

Genes affected

PRDM5 (HGNC:9349): (PR/SET domain 5) The protein encoded by this gene is a transcription factor of the PR-domain protein family. It contains a PR-domain and multiple zinc finger motifs. Transcription factors of the PR-domain family are known to be involved in cell differentiation and tumorigenesis. [provided by RefSeq, Jul 2008]

PRDM5 Gene-Disease associations (from GenCC):

• brittle cornea syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia
• brittle cornea syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• aortic disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Axenfeld-Rieger syndrome

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM5	NM_018699.4	c.177+26839C>T		intron_variant	Intron 2 of 15	ENST00000264808.8	NP_061169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM5	ENST00000264808.8	c.177+26839C>T		intron_variant	Intron 2 of 15	1	NM_018699.4	ENSP00000264808.3

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37135 AN: 151356 Hom.: 5136 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.245 AC: 37184 AN: 151474 Hom.: 5146 Cov.: 32 AF XY: 0.243 AC XY: 17992 AN XY: 73946

African (AFR) AF: 0.361 AC: 14919 AN: 41316

American (AMR) AF: 0.252 AC: 3846 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 708 AN: 3462

East Asian (EAS) AF: 0.327 AC: 1684 AN: 5152

South Asian (SAS) AF: 0.164 AC: 788 AN: 4792

European-Finnish (FIN) AF: 0.135 AC: 1399 AN: 10400

Middle Eastern (MID) AF: 0.306 AC: 88 AN: 288

European-Non Finnish (NFE) AF: 0.193 AC: 13116 AN: 67810

Other (OTH) AF: 0.252 AC: 529 AN: 2102

Alfa AF: 0.214 Hom.: 7270

Bravo AF: 0.263

Asia WGS AF: 0.258 AC: 896 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.28
PhyloP100		-0.92
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: rs180730; hg19: chr4-121801790;