1-109296211-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001010985.3(MYBPHL):c.867+23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,611,356 control chromosomes in the GnomAD database, including 796,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (71754 hom., cov: 30)
  • Exomes 𝑓: 1.0 (724920 hom.)
• Consequence: MYBPHL NM_001010985.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.388

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-109296211-T-C is Benign according to our data. Variant chr1-109296211-T-C is described in ClinVar as [Benign]. Clinvar id is 1282714.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPHL	NM_001010985.3	c.867+23A>G		intron_variant		ENST00000357155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPHL	ENST00000357155.2	c.867+23A>G		intron_variant		1	NM_001010985.3	P1
MYBPHL	ENST00000477962.1	n.150-914A>G		intron_variant, non_coding_transcript_variant		1
MYBPHL	ENST00000489706.5	n.120+23A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147535 AN: 152102 Hom.: 71710 Cov.: 30

Gnomad AFR AF: 0.896

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.981

GnomAD3 exomes AF: 0.992 AC: 248068 AN: 250074 Hom.: 123145 AF XY: 0.994 AC XY: 134438 AN XY: 135234

Gnomad AFR exome AF: 0.893

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.997 AC: 1454263 AN: 1459136 Hom.: 724920 Cov.: 46 AF XY: 0.997 AC XY: 723753 AN XY: 725880

Gnomad4 AFR exome AF: 0.893

Gnomad4 AMR exome AF: 0.995

Gnomad4 ASJ exome AF: 0.995

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.993

GnomAD4 genome AF: 0.970 AC: 147635 AN: 152220 Hom.: 71754 Cov.: 30 AF XY: 0.971 AC XY: 72244 AN XY: 74416

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.988

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.981

Alfa AF: 0.995 Hom.: 7981

Bravo AF: 0.967

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.2
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs616899; hg19: chr1-109838833;