rs388707

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001186.4(BACH1):c.1833T>C(p.Gly611=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,613,806 control chromosomes in the GnomAD database, including 161,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 19501 hom., cov: 33)

Exomes 𝑓: 0.44 ( 141877 hom. )

Consequence

BACH1
NM_001186.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.61

Variant links:

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]

BACH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 21-29342455-T-C is Benign according to our data. Variant chr21-29342455-T-C is described in ClinVar as [Benign]. Clinvar id is 3059943.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BACH1	NM_001186.4 linkuse as main transcript	c.1833T>C	p.Gly611=	synonymous_variant	5/5	ENST00000286800.8
BACH1	NM_206866.3 linkuse as main transcript	c.1833T>C	p.Gly611=	synonymous_variant	5/5
BACH1	NR_027655.3 linkuse as main transcript	n.1956-9179T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BACH1	ENST00000286800.8 linkuse as main transcript	c.1833T>C	p.Gly611=	synonymous_variant	5/5	1	NM_001186.4	P1
BACH1	ENST00000399921.5 linkuse as main transcript	c.1833T>C	p.Gly611=	synonymous_variant	5/5	1		P1
BACH1	ENST00000422809.5 linkuse as main transcript	c.472+12762T>C		intron_variant		5
BACH1	ENST00000468059.1 linkuse as main transcript	c.325+12762T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.494

AC:

75020

AN:

151886

Hom.:

19476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.595

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.489

GnomAD3 exomes

AF:

0.470

AC:

117996

AN:

251236

Hom.:

28777

AF XY:

0.468

AC XY:

63591

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.650

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.463

Gnomad SAS exome

AF:

0.583

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.436

AC:

637340

AN:

1461802

Hom.:

141877

Cov.:

AF XY:

0.439

AC XY:

319247

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.654

Gnomad4 AMR exome

AF:

0.519

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.451

Gnomad4 SAS exome

AF:

0.571

Gnomad4 FIN exome

AF:

0.369

Gnomad4 NFE exome

AF:

0.416

Gnomad4 OTH exome

AF:

0.457

GnomAD4 genome

AF:

0.494

AC:

75090

AN:

152004

Hom.:

19501

Cov.:

AF XY:

0.492

AC XY:

36567

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.647

Gnomad4 AMR

AF:

0.490

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.596

Gnomad4 FIN

AF:

0.372

Gnomad4 NFE

AF:

0.420

Gnomad4 OTH

AF:

0.491

Alfa

AF:

0.445

Hom.:

19858

Bravo

AF:

0.506

Asia WGS

AF:

0.555

AC:

1928

AN:

3478

EpiCase

AF:

0.436

EpiControl

AF:

0.423

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BACH1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

Cadd

Benign

0.17

Dann

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over