rs2284235

Positions:

• chr14-77697080-T-C
• chr14-77697080-T-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

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]

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALKBH1	NM_006020.3	c.293-2180A>G		intron_variant		ENST00000216489.8
ALKBH1	XM_047431848.1	c.293-2180A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALKBH1	ENST00000216489.8	c.293-2180A>G		intron_variant		1	NM_006020.3	P1
ZMYND19P1	ENST00000554267.1	n.490T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52623 AN: 151850 Hom.: 9413 Cov.: 32

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.: 0 AF XY: 0.457 AC XY: 9434 AN XY: 20630

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.346 AC: 52646 AN: 151968 Hom.: 9417 Cov.: 32 AF XY: 0.344 AC XY: 25515 AN XY: 74250

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.350

Alfa AF: 0.367 Hom.: 2159

Bravo AF: 0.337

Asia WGS AF: 0.308 AC: 1073 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	5.3
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs2284235; hg19: chr14-78163423; COSMIC: COSV53659445;