Genetic Variant BOLL:p.Ala267Gly (chr2-197743089-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033030.6(BOLL):c.800C>G(p.Ala267Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A267V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BOLL
NM_033030.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.17

Publications

1 publications found

Variant links:

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]

BOLL links:

ENSG00000222017 (HGNC:):

ENSG00000222017 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19473243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033030.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BOLL	NM_033030.6	MANE Select	c.800C>G	p.Ala267Gly	missense	Exon 10 of 11	NP_149019.1	Q8N9W6-1
BOLL	NM_001284361.2		c.884C>G	p.Ala295Gly	missense	Exon 11 of 12	NP_001271290.1	Q8N9W6-2
BOLL	NM_197970.3		c.836C>G	p.Ala279Gly	missense	Exon 10 of 11	NP_932074.1	Q8N9W6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BOLL	ENST00000392296.9	TSL:1 MANE Select	c.800C>G	p.Ala267Gly	missense	Exon 10 of 11	ENSP00000376116.4	Q8N9W6-1
BOLL	ENST00000433157.1	TSL:1	c.800C>G	p.Ala267Gly	missense	Exon 10 of 11	ENSP00000396099.1	Q8N9W6-1
ENSG00000222017	ENST00000409845.1	TSL:1	n.167-28768G>C		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244684

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000563

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450400

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721814

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33134

American (AMR)

AF:

0.00

AC:

AN:

42574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25936

East Asian (EAS)

AF:

0.0000256

AC:

AN:

39132

South Asian (SAS)

AF:

0.00

AC:

AN:

84476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106540

Other (OTH)

AF:

0.00

AC:

AN:

59742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0055

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

6.2

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.1

REVEL

Benign

0.081

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.017

Polyphen

0.33

Vest4

0.24

MutPred

0.36

Gain of catalytic residue at M265 (P = 0.0379)

MVP

0.25

MPC

0.55

ClinPred

0.64

GERP RS

5.3

Varity_R

0.14

gMVP

0.25

Mutation Taster

=88/12

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over