rs12070516

chr1-220654865-T-G

Variant summary

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

The NM_018650.5(MARK1):c.1988+1513T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,232 control chromosomes in the GnomAD database, including 5,361 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 0.16 (5361 hom., cov: 33)
• Consequence: MARK1 NM_018650.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

Genes affected

MARK1 (HGNC:6896): (microtubule affinity regulating kinase 1) Enables several functions, including ATP binding activity; phospholipid binding activity; and protein kinase activity. Involved in intracellular signal transduction and protein phosphorylation. Located in cytoplasm; dendrite; and plasma membrane. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARK1	NM_018650.5	c.1988+1513T>G		intron_variant		ENST00000366917.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARK1	ENST00000366917.6	c.1988+1513T>G		intron_variant		1	NM_018650.5	P3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24061 AN: 152114 Hom.: 5345 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0760

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.158 AC: 24119 AN: 152232 Hom.: 5361 Cov.: 33 AF XY: 0.154 AC XY: 11446 AN XY: 74440

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.0757

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0650

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0592 Hom.: 609

Bravo AF: 0.180

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.55
Dann	Benign	0.52

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: rs12070516; hg19: chr1-220828207;