Genetic Variant BACH1:c.1777-122G>A (chr21-29342277-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001186.4(BACH1):c.1777-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 993,708 control chromosomes in the GnomAD database, including 61,324 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 0.36 ( 10567 hom., cov: 32)

Exomes 𝑓: 0.34 ( 50757 hom. )

Consequence

BACH1
NM_001186.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.431

Publications

8 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BACH1	NM_001186.4 link	c.1777-122G>A	intron_variant	Intron 4 of 4	ENST00000286800.8	NP_001177.1	O14867
BACH1	NM_206866.3 link	c.1777-122G>A	intron_variant	Intron 4 of 4		NP_996749.1	O14867
BACH1	NR_027655.3 link	n.1956-9357G>A	intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BACH1	ENST00000286800.8 link	c.1777-122G>A	intron_variant	Intron 4 of 4	1	NM_001186.4	ENSP00000286800.3	O14867
BACH1	ENST00000399921.5 link	c.1777-122G>A	intron_variant	Intron 4 of 4	1		ENSP00000382805.1	O14867
BACH1	ENST00000422809.5 link	c.471+12584G>A	intron_variant	Intron 2 of 4	5		ENSP00000416569.1	H7C4B6
BACH1	ENST00000468059.1 link	c.324+12584G>A	intron_variant	Intron 2 of 3	3		ENSP00000470673.1	M0QZP0

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55215

AN:

151960

Hom.:

10563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.447

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.0571

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.377

GnomAD4 exome

AF:

0.339

AC:

285032

AN:

841628

Hom.:

50757

AF XY:

0.339

AC XY:

144323

AN XY:

425614

show subpopulations

African (AFR)

AF:

0.449

AC:

8919

AN:

19858

American (AMR)

AF:

0.216

AC:

5031

AN:

23272

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

6400

AN:

16262

East Asian (EAS)

AF:

0.0720

AC:

2575

AN:

35742

South Asian (SAS)

AF:

0.323

AC:

17578

AN:

54350

European-Finnish (FIN)

AF:

0.341

AC:

15264

AN:

44752

Middle Eastern (MID)

AF:

0.315

AC:

877

AN:

2782

European-Non Finnish (NFE)

AF:

0.355

AC:

215295

AN:

605846

Other (OTH)

AF:

0.338

AC:

13093

AN:

38764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

8982

17963

26945

35926

44908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5394

10788

16182

21576

26970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.363

AC:

55242

AN:

152080

Hom.:

10567

Cov.:

AF XY:

0.358

AC XY:

26574

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.446

AC:

18518

AN:

41496

American (AMR)

AF:

0.269

AC:

4110

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1360

AN:

3464

East Asian (EAS)

AF:

0.0574

AC:

298

AN:

5192

South Asian (SAS)

AF:

0.336

AC:

1618

AN:

4814

European-Finnish (FIN)

AF:

0.346

AC:

3653

AN:

10560

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.362

AC:

24622

AN:

67954

Other (OTH)

AF:

0.374

AC:

790

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1747

3494

5242

6989

8736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.366

Hom.:

7706

Bravo

AF:

0.357

Asia WGS

AF:

0.226

AC:

791

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.4

(source)

DANN

Benign

0.79

PhyloP100

0.43

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over