Genetic Variant NM_001010985.3:c.731-73_731-72delAA (chr1-109296441-ATT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010985.3(MYBPHL):c.731-73_731-72delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,348,976 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 25)

Exomes 𝑓: 0.018 ( 0 hom. )

Consequence

MYBPHL
NM_001010985.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.471

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

familial dilated cardiomyopathy
Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

MYBPHL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Variant has high frequency in the AFR (0.0302) population. However there is too low homozygotes in high coverage region: (expected more than 91, got 0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010985.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPHL	NM_001010985.3	MANE Select	c.731-73_731-72delAA		intron	N/A	NP_001010985.2	A2RUH7-1
	MYBPHL	NM_001265613.2		c.662-73_662-72delAA		intron	N/A	NP_001252542.1	A2RUH7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYBPHL	ENST00000357155.2	TSL:1 MANE Select	c.731-73_731-72delAA	intron	N/A	ENSP00000349678.1	A2RUH7-1
MYBPHL	ENST00000477962.1	TSL:1	n.150-1146_150-1145delAA	intron	N/A
MYBPHL	ENST00000968920.1		c.911-73_911-72delAA	intron	N/A	ENSP00000638979.1

Frequencies

GnomAD3 genomes

AF:

0.000318

AC:

AN:

141386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000468

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000427

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000207

Gnomad SAS

AF:

0.000225

Gnomad FIN

AF:

0.000920

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000140

Gnomad OTH

AF:

0.00104

GnomAD4 exome

AF:

0.0183

AC:

22145

AN:

1207552

Hom.:

AF XY:

0.0186

AC XY:

11167

AN XY:

601818

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0320

AC:

835

AN:

26122

American (AMR)

AF:

0.0236

AC:

601

AN:

25508

Ashkenazi Jewish (ASJ)

AF:

0.0194

AC:

399

AN:

20606

East Asian (EAS)

AF:

0.0222

AC:

742

AN:

33390

South Asian (SAS)

AF:

0.0157

AC:

1079

AN:

68638

European-Finnish (FIN)

AF:

0.0215

AC:

783

AN:

36402

Middle Eastern (MID)

AF:

0.0155

AC:

AN:

3620

European-Non Finnish (NFE)

AF:

0.0177

AC:

16690

AN:

942990

Other (OTH)

AF:

0.0191

AC:

960

AN:

50276

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.272

Heterozygous variant carriers

2206

4412

6619

8825

11031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

568

1136

1704

2272

2840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000332

AC:

AN:

141424

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

AN XY:

68426

show subpopulations

African (AFR)

AF:

0.000519

AC:

AN:

38520

American (AMR)

AF:

0.000427

AC:

AN:

14054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3308

East Asian (EAS)

AF:

0.000207

AC:

AN:

4830

South Asian (SAS)

AF:

0.000227

AC:

AN:

4408

European-Finnish (FIN)

AF:

0.000920

AC:

AN:

8700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000140

AC:

AN:

64502

Other (OTH)

AF:

0.00103

AC:

AN:

1934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over