rs4938534

Variant names:

• chr11-111404408-G-A
• rs4938534
• ENST00000515029.2:n.155+213C>T

Variant summary

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

The ENST00000515029.2(POU2AF1):​n.155+213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,050 control chromosomes in the GnomAD database, including 24,807 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 0.56 (24807 hom., cov: 32)
• Consequence: POU2AF1 ENST00000515029.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 27 publications found

Genes affected

POU2AF1 (HGNC:9211): (POU class 2 homeobox associating factor 1) Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of RNA polymerase II transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

BTG4 (HGNC:13862): (BTG anti-proliferation factor 4) The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein can induce G1 arrest in the cell cycle. [provided by RefSeq, Jul 2008]

BTG4 Gene-Disease associations (from GenCC):

• oocyte maturation defect 8

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

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTG4	XM_024448587.2	c.764+213C>T		intron_variant	Intron 6 of 7		XP_024304355.1
BTG4	XM_024448588.2	c.764+213C>T		intron_variant	Intron 7 of 8		XP_024304356.1
BTG4	XM_024448589.2	c.764+213C>T		intron_variant	Intron 6 of 7		XP_024304357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF1	ENST00000515029.2	n.155+213C>T		intron_variant	Intron 2 of 5	1
POU2AF1	ENST00000531398.1	c.22+213C>T		intron_variant	Intron 2 of 4	4		ENSP00000433527.1
POU2AF1	ENST00000525890.1	n.*232C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84871 AN: 151932 Hom.: 24800 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.558 AC: 84911 AN: 152050 Hom.: 24807 Cov.: 32 AF XY: 0.561 AC XY: 41653 AN XY: 74298

African (AFR) AF: 0.388 AC: 16073 AN: 41460

American (AMR) AF: 0.690 AC: 10544 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2145 AN: 3468

East Asian (EAS) AF: 0.492 AC: 2541 AN: 5168

South Asian (SAS) AF: 0.433 AC: 2085 AN: 4812

European-Finnish (FIN) AF: 0.654 AC: 6894 AN: 10548

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42750 AN: 67990

Other (OTH) AF: 0.589 AC: 1243 AN: 2112

Alfa AF: 0.598 Hom.: 63023

Bravo AF: 0.558

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.45
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs4938534; hg19: chr11-111275133;