rs3737296

Variant names:

• chr1-220652181-A-G
• rs3737296
• NM_018650.5:c.1736+31A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-220652181-A-G
• chr1-220652181-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018650.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK1	NM_018650.5	MANE Select	c.1736+31A>G		intron	N/A	NP_061120.3
	MARK1	NM_001286124.2		c.1736+31A>G		intron	N/A	NP_001273053.1	A0A087X0I6
	MARK1	NM_001286126.2		c.1736+31A>G		intron	N/A	NP_001273055.1	B4DIB3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK1	ENST00000366917.6	TSL:1 MANE Select	c.1736+31A>G		intron	N/A	ENSP00000355884.5	Q9P0L2-1
	MARK1	ENST00000611084.4	TSL:1	c.1736+31A>G		intron	N/A	ENSP00000483424.1	A0A087X0I6
	MARK1	ENST00000402574.5	TSL:1	c.1736+31A>G		intron	N/A	ENSP00000386017.2	B4DIB3

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

GnomAD2 exomes AF: 0.757 AC: 185368 AN: 244992 AF XY: 0.760

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 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

African (AFR) AF: 0.960 AC: 31063 AN: 32364

American (AMR) AF: 0.652 AC: 27891 AN: 42800

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 18011 AN: 24668

East Asian (EAS) AF: 0.630 AC: 24339 AN: 38620

South Asian (SAS) AF: 0.804 AC: 64152 AN: 79776

European-Finnish (FIN) AF: 0.760 AC: 39385 AN: 51836

Middle Eastern (MID) AF: 0.749 AC: 4119 AN: 5496

European-Non Finnish (NFE) AF: 0.776 AC: 825586 AN: 1064034

Other (OTH) AF: 0.782 AC: 44647 AN: 57112

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

African (AFR) AF: 0.952 AC: 39520 AN: 41528

American (AMR) AF: 0.758 AC: 11577 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2538 AN: 3468

East Asian (EAS) AF: 0.658 AC: 3400 AN: 5166

South Asian (SAS) AF: 0.792 AC: 3819 AN: 4820

European-Finnish (FIN) AF: 0.763 AC: 8071 AN: 10576

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.770 AC: 52331 AN: 67978

Other (OTH) AF: 0.807 AC: 1705 AN: 2114

Alfa AF: 0.765 Hom.: 25784

Bravo AF: 0.814

Asia WGS AF: 0.756 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.38
PhyloP100		-0.54
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: rs3737296; hg19: chr1-220825523; COSMIC: COSV65067888;