7-102460822-G-T

Variant names:

• chr7-102460822-G-T
• rs4487686
• NM_017621.4:c.124-1021C>A

Variant summary

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

The NM_017621.4(ALKBH4):​c.124-1021C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,948 control chromosomes in the GnomAD database, including 22,415 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 0.53 (22415 hom., cov: 32)
• Consequence: ALKBH4 NM_017621.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 24 publications found

Genes affected

ALKBH4 (HGNC:21900): (alkB homolog 4, lysine demethylase) Enables 2-oxoglutarate-dependent dioxygenase activity and actin binding activity. Involved in actomyosin structure organization; cleavage furrow ingression; and protein demethylation. Located in contractile ring and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017621.4. 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
	ALKBH4	NM_017621.4	MANE Select	c.124-1021C>A		intron	N/A	NP_060091.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALKBH4	ENST00000292566.4	TSL:1 MANE Select	c.124-1021C>A		intron	N/A	ENSP00000292566.3
	ALKBH4	ENST00000881811.1		c.124-2841C>A		intron	N/A	ENSP00000551870.1
	ALKBH4	ENST00000490528.1	TSL:2	n.124-1112C>A		intron	N/A	ENSP00000420362.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80348 AN: 151830 Hom.: 22426 Cov.: 32

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.529 AC: 80362 AN: 151948 Hom.: 22415 Cov.: 32 AF XY: 0.521 AC XY: 38709 AN XY: 74246

African (AFR) AF: 0.362 AC: 15005 AN: 41452

American (AMR) AF: 0.551 AC: 8405 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2495 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1957 AN: 5156

South Asian (SAS) AF: 0.469 AC: 2260 AN: 4822

European-Finnish (FIN) AF: 0.524 AC: 5521 AN: 10542

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42867 AN: 67932

Other (OTH) AF: 0.560 AC: 1182 AN: 2112

Alfa AF: 0.606 Hom.: 44014

Bravo AF: 0.529

Asia WGS AF: 0.393 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.82
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4487686; hg19: chr7-102101269;