rs231247

Variant names:

• chr4-112438547-A-G
• rs231247
• NM_025144.4:c.3252A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-112438547-A-G
• chr4-112438547-A-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_025144.4(ALPK1):​c.3252A>G​(p.Arg1084Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,613,226 control chromosomes in the GnomAD database, including 350,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35554 hom., cov: 31)
  • Exomes 𝑓: 0.65 (314887 hom.)
• Consequence: ALPK1 NM_025144.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.417
• Publications: 25 publications found

Genes affected

ALPK1 (HGNC:20917): (alpha kinase 1) This gene encodes an alpha kinase. Mice which were homozygous for disrupted copies of this gene exhibited coordination defects (PMID: 21208416). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ALPK1 Gene-Disease associations (from GenCC):

• retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 4-112438547-A-G is Benign according to our data. Variant chr4-112438547-A-G is described in ClinVar as Benign. ClinVar VariationId is 2115848.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.417 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025144.4. 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
	ALPK1	NM_025144.4	MANE Select	c.3252A>G	p.Arg1084Arg	synonymous	Exon 13 of 16	NP_079420.3
	ALPK1	NM_001102406.2		c.3252A>G	p.Arg1084Arg	synonymous	Exon 13 of 16	NP_001095876.1	Q96QP1-1
	ALPK1	NM_001253884.2		c.3018A>G	p.Arg1006Arg	synonymous	Exon 12 of 15	NP_001240813.1	Q96QP1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	ENST00000650871.1	MANE Select	c.3252A>G	p.Arg1084Arg	synonymous	Exon 13 of 16	ENSP00000498374.1	Q96QP1-1
	ALPK1	ENST00000177648.13	TSL:1	c.3252A>G	p.Arg1084Arg	synonymous	Exon 13 of 16	ENSP00000177648.9	Q96QP1-1
	ALPK1	ENST00000909431.1		c.3270A>G	p.Arg1090Arg	synonymous	Exon 13 of 16	ENSP00000579490.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103652 AN: 151882 Hom.: 35531 Cov.: 31

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.682

GnomAD2 exomes AF: 0.650 AC: 163265 AN: 251078 AF XY: 0.648

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.709

Gnomad EAS exome AF: 0.712

Gnomad FIN exome AF: 0.706

Gnomad NFE exome AF: 0.660

Gnomad OTH exome AF: 0.654

GnomAD4 exome AF: 0.655 AC: 957012 AN: 1461226 Hom.: 314887 Cov.: 51 AF XY: 0.653 AC XY: 474698 AN XY: 726918

African (AFR) AF: 0.736 AC: 24627 AN: 33448

American (AMR) AF: 0.571 AC: 25499 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 18591 AN: 26114

East Asian (EAS) AF: 0.727 AC: 28843 AN: 39688

South Asian (SAS) AF: 0.576 AC: 49644 AN: 86194

European-Finnish (FIN) AF: 0.703 AC: 37537 AN: 53400

Middle Eastern (MID) AF: 0.643 AC: 3708 AN: 5764

European-Non Finnish (NFE) AF: 0.656 AC: 728686 AN: 1111576

Other (OTH) AF: 0.661 AC: 39877 AN: 60360

GnomAD4 genome AF: 0.682 AC: 103728 AN: 152000 Hom.: 35554 Cov.: 31 AF XY: 0.682 AC XY: 50691 AN XY: 74308

African (AFR) AF: 0.734 AC: 30452 AN: 41460

American (AMR) AF: 0.619 AC: 9443 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2452 AN: 3470

East Asian (EAS) AF: 0.718 AC: 3694 AN: 5146

South Asian (SAS) AF: 0.577 AC: 2781 AN: 4822

European-Finnish (FIN) AF: 0.717 AC: 7575 AN: 10570

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45014 AN: 67950

Other (OTH) AF: 0.681 AC: 1436 AN: 2110

Alfa AF: 0.663 Hom.: 66312

Bravo AF: 0.679

Asia WGS AF: 0.585 AC: 2039 AN: 3478

EpiCase AF: 0.663

EpiControl AF: 0.654

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.7
DANN	Benign	0.64
PhyloP100		-0.42
Mutation Taster		=87/13	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: rs231247; hg19: chr4-113359703; COSMIC: COSV51589338;