Variant 1-109296296-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000357155.2(MYBPHL):c.805G>A(p.Asp269Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,613,934 control chromosomes in the GnomAD database, including 691,924 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.87 ( 58961 hom., cov: 30)

Exomes 𝑓: 0.93 ( 632963 hom. )

Consequence

MYBPHL
ENST00000357155.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.96

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.7328716E-7).

BP6

Variant 1-109296296-C-T is Benign according to our data. Variant chr1-109296296-C-T is described in ClinVar as [Benign]. Clinvar id is 1253160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.805G>A	p.Asp269Asn	missense_variant	6/9	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.805G>A	p.Asp269Asn	missense_variant	6/9	1	NM_001010985.3	ENSP00000349678	P1	A2RUH7-1
MYBPHL	ENST00000477962.1 linkuse as main transcript	n.150-999G>A		intron_variant, non_coding_transcript_variant		1
MYBPHL	ENST00000489706.5 linkuse as main transcript	n.58G>A		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.874

AC:

132861

AN:

151964

Hom.:

58931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.702

Gnomad AMI

AF:

0.905

Gnomad AMR

AF:

0.939

Gnomad ASJ

AF:

0.937

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.943

Gnomad FIN

AF:

0.959

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.932

Gnomad OTH

AF:

0.891

GnomAD3 exomes

AF:

0.928

AC:

233468

AN:

251482

Hom.:

108930

AF XY:

0.932

AC XY:

126739

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.694

Gnomad AMR exome

AF:

0.959

Gnomad ASJ exome

AF:

0.933

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.948

Gnomad FIN exome

AF:

0.960

Gnomad NFE exome

AF:

0.929

Gnomad OTH exome

AF:

0.930

GnomAD4 exome

AF:

0.930

AC:

1359175

AN:

1461852

Hom.:

632963

Cov.:

AF XY:

0.931

AC XY:

677252

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.698

Gnomad4 AMR exome

AF:

0.955

Gnomad4 ASJ exome

AF:

0.933

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.950

Gnomad4 FIN exome

AF:

0.960

Gnomad4 NFE exome

AF:

0.930

Gnomad4 OTH exome

AF:

0.926

GnomAD4 genome

AF:

0.874

AC:

132946

AN:

152082

Hom.:

58961

Cov.:

AF XY:

0.879

AC XY:

65333

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.702

Gnomad4 AMR

AF:

0.939

Gnomad4 ASJ

AF:

0.937

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.943

Gnomad4 FIN

AF:

0.959

Gnomad4 NFE

AF:

0.932

Gnomad4 OTH

AF:

0.893

Alfa

AF:

0.923

Hom.:

137398

Bravo

AF:

0.865

TwinsUK

AF:

0.923

AC:

3423

ALSPAC

AF:

0.933

AC:

3596

ESP6500AA

AF:

0.714

AC:

3148

ESP6500EA

AF:

0.935

AC:

8037

ExAC

AF:

0.922

AC:

111932

Asia WGS

AF:

0.947

AC:

3293

AN:

3478

EpiCase

AF:

0.936

EpiControl

AF:

0.935

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

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0093

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.79

MetaRNN

Benign

6.7e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.0082

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Benign

0.64

Sift4G

Benign

0.28

Polyphen

0.010

Vest4

0.13

MPC

0.22

ClinPred

0.014

GERP RS

3.3

Varity_R

0.079

gMVP

0.22

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

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