rs1599903

Variant names:

• chr3-39913575-A-C
• rs1599903
• NM_015460.4:c.110+12649A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-39913575-A-C
• chr3-39913575-A-T

Variant summary

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

The NM_015460.4(MYRIP):​c.110+12649A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,980 control chromosomes in the GnomAD database, including 19,121 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 0.49 (19121 hom., cov: 32)
• Consequence: MYRIP NM_015460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 0 publications found

Genes affected

MYRIP (HGNC:19156): (myosin VIIA and Rab interacting protein) Predicted to enable actin binding activity and myosin binding activity. Predicted to be involved in positive regulation of insulin secretion. Predicted to be located in actin cytoskeleton; dense core granule; and perinuclear region of cytoplasm. Predicted to be part of exocyst. Predicted to be active in cortical actin cytoskeleton. [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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015460.4. 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
	MYRIP	NM_015460.4	MANE Select	c.110+12649A>C		intron	N/A	NP_056275.2	Q8NFW9-1
	MYRIP	NM_001284423.2		c.110+12649A>C		intron	N/A	NP_001271352.1	Q8NFW9-1
	MYRIP	NM_001284424.2		c.110+12649A>C		intron	N/A	NP_001271353.1	Q8NFW9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRIP	ENST00000302541.11	TSL:1 MANE Select	c.110+12649A>C		intron	N/A	ENSP00000301972.6	Q8NFW9-1
	MYRIP	ENST00000444716.5	TSL:1	c.110+12649A>C		intron	N/A	ENSP00000398665.1	Q8NFW9-1
	MYRIP	ENST00000396217.7	TSL:1	c.-21+12649A>C		intron	N/A	ENSP00000379519.3	Q8NFW9-6

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74021 AN: 151862 Hom.: 19078 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.488 AC: 74131 AN: 151980 Hom.: 19121 Cov.: 32 AF XY: 0.486 AC XY: 36110 AN XY: 74278

African (AFR) AF: 0.667 AC: 27643 AN: 41442

American (AMR) AF: 0.430 AC: 6566 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1757 AN: 3466

East Asian (EAS) AF: 0.536 AC: 2772 AN: 5168

South Asian (SAS) AF: 0.435 AC: 2099 AN: 4824

European-Finnish (FIN) AF: 0.407 AC: 4299 AN: 10554

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27535 AN: 67926

Other (OTH) AF: 0.482 AC: 1018 AN: 2110

Alfa AF: 0.543 Hom.: 5863

Bravo AF: 0.501

Asia WGS AF: 0.516 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.71
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1599903;

hg19: chr3-39955066;