7-73444016-G-A

Position:

• chr7-73444016-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP4_Strong BS2

The NM_032408.4(BAZ1B):​c.3958C>T​(p.Pro1320Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: BAZ1B NM_032408.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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 Benign. Variant got -7 ACMG points.

• PP2: Missense variant where missense usually causes diseases, BAZ1B
• BP4: Computational evidence support a benign effect (MetaRNN=0.057794005).
• BS2: High AC in GnomAdExome4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAZ1B	NM_032408.4	c.3958C>T	p.Pro1320Ser	missense_variant	17/20	ENST00000339594.9
BAZ1B	NM_001370402.1	c.3958C>T	p.Pro1320Ser	missense_variant	17/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAZ1B	ENST00000339594.9	c.3958C>T	p.Pro1320Ser	missense_variant	17/20	1	NM_032408.4	P1
BAZ1B	ENST00000404251.1	c.3958C>T	p.Pro1320Ser	missense_variant	17/19	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250944 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135642

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461536 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.3
DANN	Benign	0.62
DEOGEN2	Benign	0.068	T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.18	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.27	N;N
REVEL	Benign	0.033
Sift	Benign	0.34	T;T
Sift4G	Benign	0.63	T;T
Polyphen		0.0	B;B
Vest4		0.14
MutPred		0.29		Loss of catalytic residue at P1320 (P = 0.0016);Loss of catalytic residue at P1320 (P = 0.0016);
MVP		0.36
MPC		0.21
ClinPred		0.020	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.17

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: rs782437549; hg19: chr7-72858346;