chr16-72186474-G-C

Variant names:

• chr16-72186474-G-C
• rs7186908
• XM_047434734.1:c.-862-12404C>G

Variant summary

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

The XM_047434734.1(PMFBP1):​c.-862-12404C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,924 control chromosomes in the GnomAD database, including 5,832 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 0.27 (5832 hom., cov: 31)
• Consequence: PMFBP1 XM_047434734.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 16 publications found

Genes affected

PMFBP1 (HGNC:17728): (polyamine modulated factor 1 binding protein 1) Involved in spermatogenesis. Located in sperm connecting piece. Implicated in spermatogenic failure 31. [provided by Alliance of Genome Resources, Apr 2022]

PMFBP1 Gene-Disease associations (from GenCC):

• spermatogenic failure 31

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (SAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40364 AN: 151804 Hom.: 5827 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.266 AC: 40402 AN: 151924 Hom.: 5832 Cov.: 31 AF XY: 0.266 AC XY: 19735 AN XY: 74250

African (AFR) AF: 0.379 AC: 15682 AN: 41378

American (AMR) AF: 0.219 AC: 3340 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 921 AN: 3472

East Asian (EAS) AF: 0.238 AC: 1221 AN: 5128

South Asian (SAS) AF: 0.435 AC: 2090 AN: 4810

European-Finnish (FIN) AF: 0.183 AC: 1932 AN: 10560

Middle Eastern (MID) AF: 0.328 AC: 95 AN: 290

European-Non Finnish (NFE) AF: 0.211 AC: 14377 AN: 67986

Other (OTH) AF: 0.274 AC: 578 AN: 2112

Alfa AF: 0.221 Hom.: 2113

Bravo AF: 0.268

Asia WGS AF: 0.337 AC: 1175 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	0.44
PhyloP100		-0.099

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7186908; hg19: chr16-72220373;