rs6527958

Positions:

• chrX-19978386-C-T

Variant summary

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

The NM_001367774.2(BCLAF3):​c.-34-8088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 110,321 control chromosomes in the GnomAD database, including 8,192 homozygotes. There are 10,786 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (8192 hom., 10786 hem., cov: 22)
• Consequence: BCLAF3 NM_001367774.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

Genes affected

BCLAF3 (HGNC:27413): (BCLAF1 and THRAP3 family member 3) Predicted to enable DNA binding activity and transcription coregulator activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in mitochondrion. Predicted to be part of mediator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCLAF3	NM_001367774.2	c.-34-8088G>A		intron_variant		ENST00000379682.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCLAF3	ENST00000379682.9	c.-34-8088G>A		intron_variant		5	NM_001367774.2	P1
BCLAF3	ENST00000379687.8	c.-34-8088G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 38851 AN: 110267 Hom.: 8187 Cov.: 22 AF XY: 0.330 AC XY: 10737 AN XY: 32543

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.322

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.353 AC: 38914 AN: 110321 Hom.: 8192 Cov.: 22 AF XY: 0.331 AC XY: 10786 AN XY: 32607

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0270

Gnomad4 SAS AF: 0.0748

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.326

Alfa AF: 0.287 Hom.: 2009

Bravo AF: 0.379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.54
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6527958; hg19: chrX-19996504;