11-111430057-T-G

Variant names:

• chr11-111430057-T-G
• rs4936453
• ENST00000515029.2:n.53+4935A>C

Variant summary

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

The ENST00000515029.2(POU2AF1):​n.53+4935A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,088 control chromosomes in the GnomAD database, including 9,226 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 0.35 (9226 hom., cov: 33)
• Consequence: POU2AF1 ENST00000515029.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTG4	XM_024448587.2	c.663-25335A>C		intron_variant	Intron 5 of 7		XP_024304355.1
BTG4	XM_024448588.2	c.663-25335A>C		intron_variant	Intron 6 of 8		XP_024304356.1
BTG4	XM_024448589.2	c.663-25335A>C		intron_variant	Intron 5 of 7		XP_024304357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF1	ENST00000515029.2	n.53+4935A>C		intron_variant	Intron 1 of 5	1
POU2AF1	ENST00000531398.1	c.-81+19862A>C		intron_variant	Intron 1 of 4	4		ENSP00000433527.1
POU2AF1	ENST00000525890.1	n.412+25162A>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52706 AN: 151970 Hom.: 9201 Cov.: 33

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.347 AC: 52777 AN: 152088 Hom.: 9226 Cov.: 33 AF XY: 0.350 AC XY: 25996 AN XY: 74346

African (AFR) AF: 0.391 AC: 16221 AN: 41460

American (AMR) AF: 0.362 AC: 5537 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3468

East Asian (EAS) AF: 0.288 AC: 1491 AN: 5178

South Asian (SAS) AF: 0.326 AC: 1572 AN: 4824

European-Finnish (FIN) AF: 0.396 AC: 4186 AN: 10568

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21553 AN: 67994

Other (OTH) AF: 0.338 AC: 714 AN: 2112

Alfa AF: 0.346 Hom.: 2943

Bravo AF: 0.349

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		0.055

Splicing

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

Other links and lift over

dbSNP: rs4936453; hg19: chr11-111300782;