Genetic Variant NM_006020.3:c.293-2180A>G (chr14-77697080-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006020.3(ALKBH1):c.293-2180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 186,724 control chromosomes in the GnomAD database, including 12,699 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 0.35 ( 9417 hom., cov: 32)

Exomes 𝑓: 0.45 ( 3282 hom. )

Consequence

ALKBH1
NM_006020.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.74

Publications

3 publications found

Variant links:

Genes affected

ALKBH1 (HGNC:17911): (alkB homolog 1, histone H2A dioxygenase) This gene encodes a homolog to the E. coli alkB gene product. The E. coli alkB protein is part of the adaptive response mechanism of DNA alkylation damage repair. It is involved in damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine. [provided by RefSeq, Jul 2008]

ALKBH1 links:

ZMYND19P1 (HGNC:44540): (zinc finger MYND-type containing 19 pseudogene 1)

ZMYND19P1 links:

Genome browser will be placed here

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 (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006020.3. 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
	ALKBH1	NM_006020.3	MANE Select	c.293-2180A>G		intron	N/A	NP_006011.2	Q13686

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALKBH1	ENST00000216489.8	TSL:1 MANE Select	c.293-2180A>G	intron	N/A	ENSP00000216489.3	Q13686
ALKBH1	ENST00000856894.1		c.407-2180A>G	intron	N/A	ENSP00000526953.1
ALKBH1	ENST00000856896.1		c.293-2213A>G	intron	N/A	ENSP00000526955.1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52623

AN:

151850

Hom.:

9413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.347

GnomAD4 exome

AF:

0.454

AC:

15780

AN:

34756

Hom.:

3282

Cov.:

AF XY:

0.457

AC XY:

9434

AN XY:

20630

show subpopulations

African (AFR)

AF:

0.373

AC:

448

AN:

1200

American (AMR)

AF:

0.360

AC:

1252

AN:

3478

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

288

AN:

568

East Asian (EAS)

AF:

0.382

AC:

1005

AN:

2628

South Asian (SAS)

AF:

0.390

AC:

1470

AN:

3766

European-Finnish (FIN)

AF:

0.473

AC:

1106

AN:

2336

Middle Eastern (MID)

AF:

0.342

AC:

235

AN:

688

European-Non Finnish (NFE)

AF:

0.499

AC:

9294

AN:

18642

Other (OTH)

AF:

0.470

AC:

682

AN:

1450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.636

Heterozygous variant carriers

322

645

967

1290

1612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.346

AC:

52646

AN:

151968

Hom.:

9417

Cov.:

AF XY:

0.344

AC XY:

25515

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.282

AC:

11688

AN:

41452

American (AMR)

AF:

0.305

AC:

4659

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

1565

AN:

3470

East Asian (EAS)

AF:

0.316

AC:

1630

AN:

5152

South Asian (SAS)

AF:

0.284

AC:

1366

AN:

4814

European-Finnish (FIN)

AF:

0.346

AC:

3643

AN:

10544

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.397

AC:

26994

AN:

67942

Other (OTH)

AF:

0.350

AC:

738

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1806

3612

5419

7225

9031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

516

1032

1548

2064

2580

<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:

0.365

Hom.:

2192

Bravo

AF:

0.337

Asia WGS

AF:

0.308

AC:

1073

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

5.3

(source)

DANN

Benign

0.72

PhyloP100

2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over