rs1178977

Positions:

• chr7-73442719-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032408.4(BAZ1B):​c.4094+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,612,286 control chromosomes in the GnomAD database, including 29,469 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3732 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25737 hom.)
• Consequence: BAZ1B NM_032408.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002968
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BAZ1B	NM_032408.4	c.4094+6T>C		splice_region_variant, intron_variant		ENST00000339594.9	NP_115784.1
BAZ1B	NM_001370402.1	c.4094+6T>C		splice_region_variant, intron_variant			NP_001357331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BAZ1B	ENST00000339594.9	c.4094+6T>C		splice_region_variant, intron_variant		1	NM_032408.4	ENSP00000342434.4
BAZ1B	ENST00000404251.1	c.4094+6T>C		splice_region_variant, intron_variant		2		ENSP00000385442.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31498 AN: 151908 Hom.: 3710 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.162 AC: 40684 AN: 251154 Hom.: 3717 AF XY: 0.159 AC XY: 21612 AN XY: 135720

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.0988

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.0896

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.183 AC: 267401 AN: 1460258 Hom.: 25737 Cov.: 32 AF XY: 0.180 AC XY: 131021 AN XY: 726384

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.0976

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.208 AC: 31568 AN: 152028 Hom.: 3732 Cov.: 32 AF XY: 0.204 AC XY: 15188 AN XY: 74320

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0992

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.188

Alfa AF: 0.187 Hom.: 4874

Bravo AF: 0.210

Asia WGS AF: 0.129 AC: 450 AN: 3478

EpiCase AF: 0.180

EpiControl AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.042
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: rs1178977; hg19: chr7-72857049;