1-109296441-AT-A

Variant names:

• chr1-109296441-AT-A
• rs59806839
• NM_001010985.3:c.731-72delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001010985.3(MYBPHL):​c.731-72delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 141,140 control chromosomes in the GnomAD database, including 931 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (931 hom., cov: 25)
  • Exomes 𝑓: 0.33 (238 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYBPHL NM_001010985.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.471
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-109296441-AT-A is Benign according to our data. Variant chr1-109296441-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1268940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

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.731-72delA		intron	N/A	NP_001010985.2	A2RUH7-1
	MYBPHL	NM_001265613.2		c.662-72delA		intron	N/A	NP_001252542.1	A2RUH7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPHL	ENST00000357155.2	TSL:1 MANE Select	c.731-72delA		intron	N/A	ENSP00000349678.1	A2RUH7-1
	MYBPHL	ENST00000477962.1	TSL:1	n.150-1145delA		intron	N/A
	MYBPHL	ENST00000968920.1		c.911-72delA		intron	N/A	ENSP00000638979.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 15596 AN: 141102 Hom.: 926 Cov.: 25

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0362

Gnomad NFE AF: 0.0925

Gnomad OTH AF: 0.0815

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.326 AC: 376905 AN: 1156304 Hom.: 238 AF XY: 0.329 AC XY: 188895 AN XY: 574950

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

African (AFR) AF: 0.352 AC: 8993 AN: 25572

American (AMR) AF: 0.345 AC: 8467 AN: 24536

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 6435 AN: 19680

East Asian (EAS) AF: 0.368 AC: 11792 AN: 32006

South Asian (SAS) AF: 0.344 AC: 21813 AN: 63476

European-Finnish (FIN) AF: 0.337 AC: 11731 AN: 34826

Middle Eastern (MID) AF: 0.303 AC: 1056 AN: 3490

European-Non Finnish (NFE) AF: 0.321 AC: 290520 AN: 904560

Other (OTH) AF: 0.334 AC: 16098 AN: 48158

⚠️ 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.

GnomAD4 genome AF: 0.111 AC: 15626 AN: 141140 Hom.: 931 Cov.: 25 AF XY: 0.110 AC XY: 7496 AN XY: 68302

African (AFR) AF: 0.184 AC: 7069 AN: 38480

American (AMR) AF: 0.0647 AC: 906 AN: 14012

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 82 AN: 3304

East Asian (EAS) AF: 0.0332 AC: 160 AN: 4820

South Asian (SAS) AF: 0.0327 AC: 144 AN: 4402

European-Finnish (FIN) AF: 0.114 AC: 983 AN: 8622

Middle Eastern (MID) AF: 0.0426 AC: 12 AN: 282

European-Non Finnish (NFE) AF: 0.0925 AC: 5956 AN: 64406

Other (OTH) AF: 0.0810 AC: 156 AN: 1926

Alfa AF: 0.0333 Hom.: 21

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs59806839; hg19: chr1-109839063;