rs3737296

chr1-220652181-A-Gchr1-220652181-A-T

Variant summary

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

The NM_018650.5(MARK1):c.1736+31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 1,548,832 control chromosomes in the GnomAD database, including 470,088 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 0.81 (51198 hom., cov: 31)
  • Exomes 𝑓: 0.77 (418890 hom.)
• Consequence: MARK1 NM_018650.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARK1	NM_018650.5	c.1736+31A>G		intron_variant		ENST00000366917.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARK1	ENST00000366917.6	c.1736+31A>G		intron_variant		1	NM_018650.5	P3

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123853 AN: 152008 Hom.: 51135 Cov.: 31

Gnomad AFR AF: 0.952

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.803

GnomAD3 exomes AF: 0.757 AC: 185368 AN: 244992 Hom.: 70913 AF XY: 0.760 AC XY: 100699 AN XY: 132558

Gnomad AFR exome AF: 0.956

Gnomad AMR exome AF: 0.641

Gnomad ASJ exome AF: 0.727

Gnomad EAS exome AF: 0.664

Gnomad SAS exome AF: 0.803

Gnomad FIN exome AF: 0.756

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.765

GnomAD4 exome AF: 0.773 AC: 1079193 AN: 1396706 Hom.: 418890 Cov.: 26 AF XY: 0.773 AC XY: 531998 AN XY: 688538

Gnomad4 AFR exome AF: 0.960

Gnomad4 AMR exome AF: 0.652

Gnomad4 ASJ exome AF: 0.730

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.804

Gnomad4 FIN exome AF: 0.760

Gnomad4 NFE exome AF: 0.776

Gnomad4 OTH exome AF: 0.782

GnomAD4 genome AF: 0.815 AC: 123976 AN: 152126 Hom.: 51198 Cov.: 31 AF XY: 0.811 AC XY: 60276 AN XY: 74354

Gnomad4 AFR AF: 0.952

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.807

Alfa AF: 0.757 Hom.: 15808

Bravo AF: 0.814

Asia WGS AF: 0.756 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.50
Dann	Benign	0.38

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: rs3737296; hg19: chr1-220825523; COSMIC: COSV65067888;