3-40209791-G-A

Position:

• chr3-40209791-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.1666-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,594,510 control chromosomes in the GnomAD database, including 209,185 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 0.40 (15010 hom., cov: 31)
  • Exomes 𝑓: 0.51 (194175 hom.)
• Consequence: MYRIP NM_015460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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]

EIF1B-AS1 (HGNC:44555): (EIF1B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRIP	NM_015460.4	c.1666-63G>A		intron_variant		ENST00000302541.11	NP_056275.2
EIF1B-AS1	NR_033965.1	n.537-35069C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11	c.1666-63G>A		intron_variant		1	NM_015460.4	ENSP00000301972	P1
EIF1B-AS1	ENST00000657703.1	n.90+91446C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61193 AN: 151826 Hom.: 15004 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.509 AC: 734572 AN: 1442564 Hom.: 194175 AF XY: 0.505 AC XY: 361838 AN XY: 716200

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.403 AC: 61207 AN: 151946 Hom.: 15010 Cov.: 31 AF XY: 0.404 AC XY: 30011 AN XY: 74226

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.388

Alfa AF: 0.472 Hom.: 2974

Bravo AF: 0.381

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.54

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: rs2679798; hg19: chr3-40251282; COSMIC: COSV56869895; COSMIC: COSV56869895;