1-203171426-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004997.3(MYBPH):c.750G>C(p.Val250=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000699 in 1,613,960 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (2 hom.)
• Consequence: MYBPH NM_004997.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.247

Genes affected

MYBPH (HGNC:7552): (myosin binding protein H) Predicted to be a structural constituent of muscle. Predicted to be involved in regulation of striated muscle contraction. Predicted to be located in myosin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 1-203171426-C-G is Benign according to our data. Variant chr1-203171426-C-G is described in ClinVar as [Benign]. Clinvar id is 732636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.247 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPH	NM_004997.3	c.750G>C	p.Val250=	synonymous_variant	5/11	ENST00000255416.9
MYBPH	XM_047421205.1	c.873G>C	p.Val291=	synonymous_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPH	ENST00000255416.9	c.750G>C	p.Val250=	synonymous_variant	5/11	1	NM_004997.3	P1

Frequencies

GnomAD3 genomes AF: 0.00259 AC: 395 AN: 152240 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00808

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00103 AC: 259 AN: 250896 Hom.: 1 AF XY: 0.000863 AC XY: 117 AN XY: 135648

Gnomad AFR exome AF: 0.00764

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00607

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000501 AC: 732 AN: 1461602 Hom.: 2 Cov.: 32 AF XY: 0.000480 AC XY: 349 AN XY: 727138

Gnomad4 AFR exome AF: 0.00845

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00662

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00260 AC: 396 AN: 152358 Hom.: 2 Cov.: 32 AF XY: 0.00227 AC XY: 169 AN XY: 74510

Gnomad4 AFR AF: 0.00810

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00161 Hom.: 0

Bravo AF: 0.00314

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000356

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

Invitae

Apr 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	2.3
Dann	Benign	0.57

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: rs12070378; hg19: chr1-203140554;