Variant 3-40167243-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_015460.4(MYRIP):c.729+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000738 in 1,614,068 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 5 hom. )

Consequence

MYRIP
NM_015460.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.0005021

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.146

Variant links:

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]

MYRIP links:

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

EIF1B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 3-40167243-G-A is Benign according to our data. Variant chr3-40167243-G-A is described in ClinVar as [Benign]. Clinvar id is 786875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRIP	NM_015460.4 linkuse as main transcript	c.729+4G>A		splice_donor_region_variant, intron_variant		ENST00000302541.11	NP_056275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11 linkuse as main transcript	c.729+4G>A		splice_donor_region_variant, intron_variant		1	NM_015460.4	ENSP00000301972	P1	Q8NFW9-1
EIF1B-AS1	ENST00000657703.1 linkuse as main transcript	n.91-49507C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00399

AC:

608

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00102

AC:

256

AN:

249970

Hom.:

AF XY:

0.000725

AC XY:

AN XY:

135156

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.000397

AC:

581

AN:

1461722

Hom.:

Cov.:

AF XY:

0.000340

AC XY:

247

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.00400

AC:

610

AN:

152346

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.00449

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00050

dbscSNV1_RF

Benign

0.046

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over