Variant 1-109296778-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001010985.3(MYBPHL):c.730+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,614,012 control chromosomes in the GnomAD database, including 5,180 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 516 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4664 hom. )

Consequence

MYBPHL
NM_001010985.3 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.8413

Clinical Significance

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

Conservation

PhyloP100: 2.00

Variant links:

Genes affected

MYBPHL (HGNC:30434): (myosin binding protein H like) This gene encodes a protein with two immunoglobulin superfamily domains and a fibronectin 3 domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

MYBPHL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 1-109296778-C-T is Benign according to our data. Variant chr1-109296778-C-T is described in ClinVar as [Benign]. Clinvar id is 1289852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPHL	NM_001010985.3 linkuse as main transcript	c.730+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000357155.2	NP_001010985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPHL	ENST00000357155.2 linkuse as main transcript	c.730+5G>A		splice_donor_5th_base_variant, intron_variant		1	NM_001010985.3	ENSP00000349678	P1	A2RUH7-1
MYBPHL	ENST00000477962.1 linkuse as main transcript	n.150-1481G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0782

AC:

11894

AN:

152074

Hom.:

516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0949

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.0417

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.0332

Gnomad SAS

AF:

0.0314

Gnomad FIN

AF:

0.0892

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0840

Gnomad OTH

AF:

0.0524

GnomAD3 exomes

AF:

0.0636

AC:

15978

AN:

251296

Hom.:

638

AF XY:

0.0630

AC XY:

8554

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0977

Gnomad AMR exome

AF:

0.0251

Gnomad ASJ exome

AF:

0.0212

Gnomad EAS exome

AF:

0.0347

Gnomad SAS exome

AF:

0.0333

Gnomad FIN exome

AF:

0.0857

Gnomad NFE exome

AF:

0.0830

Gnomad OTH exome

AF:

0.0593

GnomAD4 exome

AF:

0.0756

AC:

110581

AN:

1461820

Hom.:

4664

Cov.:

AF XY:

0.0744

AC XY:

54140

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0959

Gnomad4 AMR exome

AF:

0.0264

Gnomad4 ASJ exome

AF:

0.0197

Gnomad4 EAS exome

AF:

0.0375

Gnomad4 SAS exome

AF:

0.0337

Gnomad4 FIN exome

AF:

0.0832

Gnomad4 NFE exome

AF:

0.0832

Gnomad4 OTH exome

AF:

0.0700

GnomAD4 genome

AF:

0.0782

AC:

11907

AN:

152192

Hom.:

516

Cov.:

AF XY:

0.0777

AC XY:

5783

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0950

Gnomad4 AMR

AF:

0.0416

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.0327

Gnomad4 SAS

AF:

0.0315

Gnomad4 FIN

AF:

0.0892

Gnomad4 NFE

AF:

0.0840

Gnomad4 OTH

AF:

0.0523

Alfa

AF:

0.0798

Hom.:

285

Bravo

AF:

0.0756

Asia WGS

AF:

0.0510

AC:

175

AN:

3478

EpiCase

AF:

0.0709

EpiControl

AF:

0.0689

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	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 28008009) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.84

dbscSNV1_RF

Benign

0.54

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