rs17007991

chr1-220583041-T-C

Variant summary

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

The NM_018650.5(MARK1):c.309+1923T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 152,218 control chromosomes in the GnomAD database, including 999 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 0.065 (999 hom., cov: 31)
• Consequence: MARK1 NM_018650.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARK1	NM_018650.5	c.309+1923T>C		intron_variant		ENST00000366917.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARK1	ENST00000366917.6	c.309+1923T>C		intron_variant		1	NM_018650.5	P3

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9835 AN: 152100 Hom.: 990 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0649 AC: 9876 AN: 152218 Hom.: 999 Cov.: 31 AF XY: 0.0628 AC XY: 4672 AN XY: 74428

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000956

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0240 Hom.: 149

Bravo AF: 0.0739

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.26
Dann	Benign	0.80

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: rs17007991; hg19: chr1-220756383;