3-40008784-G-A

Position:

• chr3-40008784-G-A

Variant summary

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

The NM_015460.4(MYRIP):​c.111-35266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,234 control chromosomes in the GnomAD database, including 1,358 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 0.10 (1358 hom., cov: 32)
• Consequence: MYRIP NM_015460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRIP	NM_015460.4	c.111-35266G>A		intron_variant		ENST00000302541.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRIP	ENST00000302541.11	c.111-35266G>A		intron_variant		1	NM_015460.4	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15306 AN: 152116 Hom.: 1337 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0956

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

GnomAD4 genome AF: 0.101 AC: 15385 AN: 152234 Hom.: 1358 Cov.: 32 AF XY: 0.100 AC XY: 7442 AN XY: 74424

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0612

Gnomad4 NFE AF: 0.0414

Gnomad4 OTH AF: 0.0965

Alfa AF: 0.0531 Hom.: 702

Bravo AF: 0.109

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.70

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: rs6791790; hg19: chr3-40050275;