rs17007991

Variant names:

• chr1-220583041-T-C
• rs17007991
• NM_018650.5:c.309+1923T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366917.6(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 ENST00000366917.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366917.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK1	NM_018650.5	MANE Select	c.309+1923T>C		intron	N/A	NP_061120.3
	MARK1	NM_001286124.2		c.309+1923T>C		intron	N/A	NP_001273053.1
	MARK1	NM_001286126.2		c.309+1923T>C		intron	N/A	NP_001273055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK1	ENST00000366917.6	TSL:1 MANE Select	c.309+1923T>C		intron	N/A	ENSP00000355884.5
	MARK1	ENST00000611084.4	TSL:1	c.309+1923T>C		intron	N/A	ENSP00000483424.1
	MARK1	ENST00000402574.5	TSL:1	c.309+1923T>C		intron	N/A	ENSP00000386017.2

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

African (AFR) AF: 0.224 AC: 9291 AN: 41498

American (AMR) AF: 0.0248 AC: 380 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000956 AC: 65 AN: 68022

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0235 Hom.: 227

Bravo AF: 0.0739

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.80
PhyloP100		-1.1
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: rs17007991; hg19: chr1-220756383;