1-109296441-ATTTTT-ATTT

Variant names:

• chr1-109296441-ATT-A
• rs59806839
• NM_001010985.3:c.731-73_731-72delAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0183 (22145/1207552) while in subpopulation AFR AF= 0.032 (835/26122). AF 95% confidence interval is 0.0302. There are 0 homozygotes in gnomad4_exome. There are 11167 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPHL	NM_001010985.3	c.731-73_731-72delAA		intron_variant	Intron 5 of 8	ENST00000357155.2	NP_001010985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPHL	ENST00000357155.2	c.731-73_731-72delAA		intron_variant	Intron 5 of 8	1	NM_001010985.3	ENSP00000349678.1
MYBPHL	ENST00000477962.1	n.150-1146_150-1145delAA		intron_variant	Intron 1 of 3	1
MYBPHL	ENST00000489706.5	n.-90_-89delAA		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000318 AC: 45 AN: 141386 Hom.: 0 Cov.: 25

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.: 0 AF XY: 0.0186 AC XY: 11167 AN XY: 601818

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.0194

Gnomad4 EAS exome AF: 0.0222

Gnomad4 SAS exome AF: 0.0157

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0191

GnomAD4 genome AF: 0.000332 AC: 47 AN: 141424 Hom.: 0 Cov.: 25 AF XY: 0.000409 AC XY: 28 AN XY: 68426

Gnomad4 AFR AF: 0.000519

Gnomad4 AMR AF: 0.000427

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000207

Gnomad4 SAS AF: 0.000227

Gnomad4 FIN AF: 0.000920

Gnomad4 NFE AF: 0.000140

Gnomad4 OTH AF: 0.00103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs59806839; hg19: chr1-109839063;