rs700651

Variant names:

• chr2-197766990-G-A
• rs700651
• NM_033030.6:c.481-387C>T

Variant summary

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

The NM_033030.6(BOLL):​c.481-387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 151,872 control chromosomes in the GnomAD database, including 40,654 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 0.72 (40654 hom., cov: 32)
• Consequence: BOLL NM_033030.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 53 publications found

Genes affected

BOLL (HGNC:14273): (boule homolog, RNA binding protein) This gene belongs to the DAZ gene family required for germ cell development. It encodes an RNA-binding protein which is more similar to Drosophila Boule than to human proteins encoded by genes DAZ (deleted in azoospermia) or DAZL (deleted in azoospermia-like). Loss of this gene function results in the absence of sperm in semen (azoospermia). Histological studies demonstrated that the primary defect is at the meiotic G2/M transition. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000222017 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BOLL	NM_033030.6	c.481-387C>T		intron_variant	Intron 6 of 10	ENST00000392296.9	NP_149019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BOLL	ENST00000392296.9	c.481-387C>T		intron_variant	Intron 6 of 10	1	NM_033030.6	ENSP00000376116.4

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109534 AN: 151754 Hom.: 40609 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.722 AC: 109633 AN: 151872 Hom.: 40654 Cov.: 32 AF XY: 0.719 AC XY: 53337 AN XY: 74218

African (AFR) AF: 0.898 AC: 37301 AN: 41528

American (AMR) AF: 0.650 AC: 9893 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2514 AN: 3466

East Asian (EAS) AF: 0.502 AC: 2594 AN: 5164

South Asian (SAS) AF: 0.655 AC: 3159 AN: 4822

European-Finnish (FIN) AF: 0.599 AC: 6318 AN: 10552

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45403 AN: 67804

Other (OTH) AF: 0.738 AC: 1554 AN: 2106

Alfa AF: 0.687 Hom.: 81074

Bravo AF: 0.733

Asia WGS AF: 0.595 AC: 2073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.55
PhyloP100		0.18
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: rs700651; hg19: chr2-198631714;