rs11213927

Variant names:

• chr11-111492436-C-T
• rs11213927
• NM_017589.4:c.662+2727G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017589.4(BTG4):​c.662+2727G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 152,240 control chromosomes in the GnomAD database, including 123 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 0.039 (123 hom., cov: 32)
• Consequence: BTG4 NM_017589.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 1 publications found

Genes affected

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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0388 (5908/152240) while in subpopulation NFE AF = 0.0457 (3105/68014). AF 95% confidence interval is 0.0443. There are 123 homozygotes in GnomAd4. There are 2819 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 123 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTG4	NM_017589.4	c.662+2727G>A		intron_variant	Intron 5 of 5		NP_060059.1
BTG4	XM_024448587.2	c.662+2727G>A		intron_variant	Intron 5 of 7		XP_024304355.1
BTG4	XM_024448588.2	c.662+2727G>A		intron_variant	Intron 6 of 8		XP_024304356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTG4	ENST00000356018.6	c.662+2727G>A		intron_variant	Intron 5 of 5	5		ENSP00000348300.2

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5907 AN: 152122 Hom.: 124 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0292

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0493

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

GnomAD4 genome AF: 0.0388 AC: 5908 AN: 152240 Hom.: 123 Cov.: 32 AF XY: 0.0379 AC XY: 2819 AN XY: 74436

African (AFR) AF: 0.0348 AC: 1445 AN: 41542

American (AMR) AF: 0.0291 AC: 445 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4822

European-Finnish (FIN) AF: 0.0496 AC: 526 AN: 10602

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0457 AC: 3105 AN: 68014

Other (OTH) AF: 0.0488 AC: 103 AN: 2110

Alfa AF: 0.0438 Hom.: 395

Bravo AF: 0.0385

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.67
PhyloP100		0.0060
Mutation Taster		=100/0	polymorphism

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: rs11213927; hg19: chr11-111363161;