1-220589182-C-T

Variant names:

• chr1-220589182-C-T
• rs12740310
• NM_018650.5:c.309+8064C>T

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MARK1	NM_018650.5	c.309+8064C>T		intron_variant	Intron 3 of 17	ENST00000366917.6	NP_061120.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARK1	ENST00000366917.6	c.309+8064C>T		intron_variant	Intron 3 of 17	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

African (AFR) AF: 0.0176 AC: 731 AN: 41568

American (AMR) AF: 0.0588 AC: 900 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4826

European-Finnish (FIN) AF: 0.0368 AC: 390 AN: 10612

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0852 AC: 5792 AN: 68008

Other (OTH) AF: 0.0670 AC: 141 AN: 2106

Alfa AF: 0.0700 Hom.: 783

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
PhyloP100		-0.27
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: rs12740310; hg19: chr1-220762524;