21-29473553-C-T

Position:

• chr21-29473553-C-T

Variant summary

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

The ENST00000468059.1(BACH1):​c.325-124017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,152 control chromosomes in the GnomAD database, including 3,762 homozygotes. 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 0.18 (3762 hom., cov: 32)
• Consequence: BACH1 ENST00000468059.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

Genes affected

BACH1 (HGNC:935): (BTB domain and CNC homolog 1) This gene encodes a transcription factor that belongs to the cap'n'collar type of basic region leucine zipper factor family (CNC-bZip). The encoded protein contains broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domains, which is atypical of CNC-bZip family members. These BTB/POZ domains facilitate protein-protein interactions and formation of homo- and/or hetero-oligomers. When this encoded protein forms a heterodimer with MafK, it functions as a repressor of Maf recognition element (MARE) and transcription is repressed. Multiple alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, May 2009]

LOC107985486 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107985486	XR_001754998.2	n.15655C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACH1	ENST00000422809.5	c.472-108759C>T		intron_variant		5		ENSP00000416569.1
BACH1	ENST00000468059.1	c.325-124017C>T		intron_variant		3		ENSP00000470673.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27737 AN: 152034 Hom.: 3742 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.183 AC: 27797 AN: 152152 Hom.: 3762 Cov.: 32 AF XY: 0.177 AC XY: 13192 AN XY: 74388

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.00250

Gnomad4 SAS AF: 0.0595

Gnomad4 FIN AF: 0.0898

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.175

Alfa AF: 0.118 Hom.: 1315

Bravo AF: 0.194

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8132309; hg19: chr21-30845873;