rs1178977

Variant names:

• chr7-73442719-A-G
• rs1178977
• NM_032408.4:c.4094+6T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 67 publications found

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]

BAZ1B Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BAZ1B	NM_032408.4	c.4094+6T>C		splice_region_variant, intron_variant	Intron 18 of 19	ENST00000339594.9	NP_115784.1
BAZ1B	NM_001370402.1	c.4094+6T>C		splice_region_variant, intron_variant	Intron 18 of 18		NP_001357331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAZ1B	ENST00000339594.9	c.4094+6T>C		splice_region_variant, intron_variant	Intron 18 of 19	1	NM_032408.4	ENSP00000342434.4
BAZ1B	ENST00000404251.1	c.4094+6T>C		splice_region_variant, intron_variant	Intron 18 of 18	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

GnomAD2 exomes AF: 0.162 AC: 40684 AN: 251154 AF XY: 0.159

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 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

African (AFR) AF: 0.308 AC: 10317 AN: 33454

American (AMR) AF: 0.103 AC: 4609 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4078 AN: 26114

East Asian (EAS) AF: 0.0976 AC: 3873 AN: 39670

South Asian (SAS) AF: 0.112 AC: 9635 AN: 86226

European-Finnish (FIN) AF: 0.171 AC: 9144 AN: 53390

Middle Eastern (MID) AF: 0.189 AC: 1053 AN: 5582

European-Non Finnish (NFE) AF: 0.193 AC: 213851 AN: 1110802

Other (OTH) AF: 0.180 AC: 10841 AN: 60314

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

African (AFR) AF: 0.306 AC: 12674 AN: 41446

American (AMR) AF: 0.140 AC: 2134 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3470

East Asian (EAS) AF: 0.0992 AC: 511 AN: 5152

South Asian (SAS) AF: 0.111 AC: 536 AN: 4812

European-Finnish (FIN) AF: 0.159 AC: 1679 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12889 AN: 67956

Other (OTH) AF: 0.188 AC: 398 AN: 2112

Alfa AF: 0.191 Hom.: 11595

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
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1178977; hg19: chr7-72857049;