rs2832270

Positions:

• chr21-29222211-G-A

Variant summary

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

The NR_027072.2(LINC00189):​n.767+27951G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,160 control chromosomes in the GnomAD database, including 2,185 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 0.14 (2185 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LINC00189 NR_027072.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

Genes affected

LINC00189 (HGNC:18461): (long intergenic non-protein coding RNA 189)

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]

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 = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINC00189	NR_027072.2	n.767+27951G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINC00189	ENST00000447125.5	n.561+27951G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21743 AN: 152042 Hom.: 2169 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0636

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0967

Gnomad OTH AF: 0.136

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.143 AC: 21779 AN: 152160 Hom.: 2185 Cov.: 32 AF XY: 0.139 AC XY: 10361 AN XY: 74394

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.0830

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.0614

Gnomad4 FIN AF: 0.0695

Gnomad4 NFE AF: 0.0967

Gnomad4 OTH AF: 0.135

Alfa AF: 0.103 Hom.: 554

Bravo AF: 0.152

Asia WGS AF: 0.0810 AC: 286 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	0.30
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2832270; hg19: chr21-30594532;