rs12936694

Positions:

• chr17-18196648-A-G

Variant summary

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

The NM_017758.4(ALKBH5):​c.851+1613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,170 control chromosomes in the GnomAD database, including 9,037 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 0.33 (9037 hom., cov: 33)
• Consequence: ALKBH5 NM_017758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

Genes affected

ALKBH5 (HGNC:25996): (alkB homolog 5, RNA demethylase) Enables mRNA N6-methyladenosine dioxygenase activity. Involved in RNA metabolic process; mRNA export from nucleus; and response to hypoxia. Located in Golgi apparatus; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALKBH5	NM_017758.4	c.851+1613A>G		intron_variant		ENST00000399138.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALKBH5	ENST00000399138.5	c.851+1613A>G		intron_variant		2	NM_017758.4	P1
ALKBH5	ENST00000541285.1	c.-173+1613A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50233 AN: 152052 Hom.: 9035 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50248 AN: 152170 Hom.: 9037 Cov.: 33 AF XY: 0.323 AC XY: 24056 AN XY: 74390

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.0961

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.325

Alfa AF: 0.388 Hom.: 23174

Bravo AF: 0.317

Asia WGS AF: 0.162 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.037
DANN	Benign	0.57

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: rs12936694; hg19: chr17-18099962; COSMIC: COSV67686854;