1-220589182-C-T

Position:

• chr1-220589182-C-T

Variant summary

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

The NM_018650.5(MARK1):​c.309+8064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 152,258 control chromosomes in the GnomAD database, including 317 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 0.055 (317 hom., cov: 32)
• Consequence: MARK1 NM_018650.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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]

MARK1 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.0833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MARK1	NM_018650.5	c.309+8064C>T		intron_variant		ENST00000366917.6	NP_061120.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARK1	ENST00000366917.6	c.309+8064C>T		intron_variant		1	NM_018650.5	ENSP00000355884.5

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8374 AN: 152140 Hom.: 317 Cov.: 32

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0677

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

GnomAD4 genome AF: 0.0550 AC: 8371 AN: 152258 Hom.: 317 Cov.: 32 AF XY: 0.0506 AC XY: 3766 AN XY: 74440

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.0588

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.0670

Alfa AF: 0.0777 Hom.: 532

Bravo AF: 0.0565

Asia WGS AF: 0.00866 AC: 30 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	1.8
DANN	Benign	0.45

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: rs12740310; hg19: chr1-220762524;