7-73442216-C-T

Position:

• chr7-73442216-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_032408.4(BAZ1B):​c.4432G>A​(p.Gly1478Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,395,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: BAZ1B NM_032408.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40

Genes affected

BAZ1B (HGNC:961): (bromodomain adjacent to zinc finger domain 1B) This gene encodes a member of the bromodomain protein family. The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, BAZ1B
• BP4: Computational evidence support a benign effect (MetaRNN=0.16174361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAZ1B	NM_032408.4	c.4432G>A	p.Gly1478Arg	missense_variant	19/20	ENST00000339594.9
BAZ1B	NM_001370402.1	c.4432G>A	p.Gly1478Arg	missense_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAZ1B	ENST00000339594.9	c.4432G>A	p.Gly1478Arg	missense_variant	19/20	1	NM_032408.4	P1
BAZ1B	ENST00000404251.1	c.4432G>A	p.Gly1478Arg	missense_variant	19/19	2		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1395032 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 693960

Gnomad4 AFR exome AF: 0.0000319

Gnomad4 AMR exome AF: 0.0000234

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000179

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2023

The c.4432G>A (p.G1478R) alteration is located in exon 19 (coding exon 19) of the BAZ1B gene. This alteration results from a G to A substitution at nucleotide position 4432, causing the glycine (G) at amino acid position 1478 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	0.036
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.90	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.083
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.046	B;B
Vest4		0.32
MutPred		0.23		Gain of methylation at K1482 (P = 0.0314);Gain of methylation at K1482 (P = 0.0314);
MVP		0.56
MPC		0.74
ClinPred		0.66	D
GERP RS		5.5
Varity_R		0.41
gMVP		0.27

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

LitVar

Other links and lift over

dbSNP: rs940869911; hg19: chr7-72856546;