1-109296770-A-G

Position:

• chr1-109296770-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001010985.3(MYBPHL):​c.730+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 1,613,766 control chromosomes in the GnomAD database, including 637,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (47873 hom., cov: 31)
  • Exomes 𝑓: 0.89 (589900 hom.)
• Consequence: MYBPHL NM_001010985.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-109296770-A-G is Benign according to our data. Variant chr1-109296770-A-G is described in ClinVar as [Benign]. Clinvar id is 1180903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPHL	NM_001010985.3	c.730+13T>C		intron_variant		ENST00000357155.2	NP_001010985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPHL	ENST00000357155.2	c.730+13T>C		intron_variant		1	NM_001010985.3	ENSP00000349678	P1
MYBPHL	ENST00000477962.1	n.150-1473T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114436 AN: 151944 Hom.: 47863 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.826

GnomAD3 exomes AF: 0.882 AC: 221455 AN: 251220 Hom.: 100393 AF XY: 0.892 AC XY: 121070 AN XY: 135758

Gnomad AFR exome AF: 0.333

Gnomad AMR exome AF: 0.944

Gnomad ASJ exome AF: 0.963

Gnomad EAS exome AF: 0.966

Gnomad SAS exome AF: 0.922

Gnomad FIN exome AF: 0.912

Gnomad NFE exome AF: 0.902

Gnomad OTH exome AF: 0.909

GnomAD4 exome AF: 0.894 AC: 1306233 AN: 1461702 Hom.: 589900 Cov.: 45 AF XY: 0.896 AC XY: 651608 AN XY: 727166

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.939

Gnomad4 ASJ exome AF: 0.964

Gnomad4 EAS exome AF: 0.963

Gnomad4 SAS exome AF: 0.921

Gnomad4 FIN exome AF: 0.915

Gnomad4 NFE exome AF: 0.902

Gnomad4 OTH exome AF: 0.877

GnomAD4 genome AF: 0.753 AC: 114463 AN: 152064 Hom.: 47873 Cov.: 31 AF XY: 0.759 AC XY: 56397 AN XY: 74352

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.968

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.925

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.828

Alfa AF: 0.840 Hom.: 10049

Bravo AF: 0.734

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.17

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: rs604349; hg19: chr1-109839392;