rs411697

Variant names:

• chr21-29342277-G-A
• rs411697
• NM_001186.4:c.1777-122G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-29342277-G-A
• chr21-29342277-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431
• Publications: 8 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001186.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH1	NM_001186.4	MANE Select	c.1777-122G>A		intron	N/A	NP_001177.1	O14867
	BACH1	NM_206866.3		c.1777-122G>A		intron	N/A	NP_996749.1	O14867
	BACH1	NR_027655.3		n.1956-9357G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACH1	ENST00000286800.8	TSL:1 MANE Select	c.1777-122G>A		intron	N/A	ENSP00000286800.3	O14867
	BACH1	ENST00000399921.5	TSL:1	c.1777-122G>A		intron	N/A	ENSP00000382805.1	O14867
	BACH1	ENST00000888449.1		c.1912-122G>A		intron	N/A	ENSP00000558508.1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55215 AN: 151960 Hom.: 10563 Cov.: 32

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

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

GnomAD4 genome AF: 0.363 AC: 55242 AN: 152080 Hom.: 10567 Cov.: 32 AF XY: 0.358 AC XY: 26574 AN XY: 74326

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.4
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs411697;

hg19: chr21-30714598;