1-109296441-ATTTTT-ATTTTTT

Variant names:

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

Variant summary

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

The NM_001010985.3(MYBPHL):​c.731-72dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 1,371,524 control chromosomes in the GnomAD database, including 413 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (365 hom., cov: 25)
  • Exomes 𝑓: 0.095 (48 hom.)
• 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-A-AT is Benign according to our data. Variant chr1-109296441-A-AT is described in ClinVar as Benign. ClinVar VariationId is 1238412.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0773 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.731-72dupA		intron	N/A	NP_001010985.2	A2RUH7-1
	MYBPHL	NM_001265613.2		c.662-72dupA		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.731-72_731-71insA		intron	N/A	ENSP00000349678.1	A2RUH7-1
	MYBPHL	ENST00000477962.1	TSL:1	n.150-1145_150-1144insA		intron	N/A
	MYBPHL	ENST00000968920.1		c.911-72_911-71insA		intron	N/A	ENSP00000638979.1

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 9955 AN: 141450 Hom.: 365 Cov.: 25

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.0916

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.0647

Gnomad EAS AF: 0.00330

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.0691

Gnomad NFE AF: 0.0783

Gnomad OTH AF: 0.0691

GnomAD4 exome AF: 0.0953 AC: 117254 AN: 1230038 Hom.: 48 AF XY: 0.0934 AC XY: 57273 AN XY: 613406

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

African (AFR) AF: 0.0920 AC: 2445 AN: 26576

American (AMR) AF: 0.0520 AC: 1372 AN: 26392

Ashkenazi Jewish (ASJ) AF: 0.0837 AC: 1772 AN: 21170

East Asian (EAS) AF: 0.0398 AC: 1374 AN: 34508

South Asian (SAS) AF: 0.0765 AC: 5386 AN: 70414

European-Finnish (FIN) AF: 0.0554 AC: 2068 AN: 37358

Middle Eastern (MID) AF: 0.0871 AC: 324 AN: 3720

European-Non Finnish (NFE) AF: 0.102 AC: 97931 AN: 958542

Other (OTH) AF: 0.0892 AC: 4582 AN: 51358

⚠️ 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: 0.0703 AC: 9950 AN: 141486 Hom.: 365 Cov.: 25 AF XY: 0.0683 AC XY: 4675 AN XY: 68462

African (AFR) AF: 0.0796 AC: 3068 AN: 38526

American (AMR) AF: 0.0428 AC: 601 AN: 14056

Ashkenazi Jewish (ASJ) AF: 0.0647 AC: 214 AN: 3308

East Asian (EAS) AF: 0.00331 AC: 16 AN: 4830

South Asian (SAS) AF: 0.0808 AC: 356 AN: 4408

European-Finnish (FIN) AF: 0.0470 AC: 410 AN: 8728

Middle Eastern (MID) AF: 0.0709 AC: 20 AN: 282

European-Non Finnish (NFE) AF: 0.0783 AC: 5051 AN: 64528

Other (OTH) AF: 0.0687 AC: 133 AN: 1936

Alfa AF: 0.0170 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;