1-203169018-G-A

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.1305C>T(p.Gly435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,613,716 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 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (2 hom.)
• Consequence: MYBPH NM_004997.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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=-0.63).
• BP6: Variant 1-203169018-G-A is Benign according to our data. Variant chr1-203169018-G-A is described in ClinVar as [Benign]. Clinvar id is 732635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.26 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.1305C>T	p.Gly435=	synonymous_variant	9/11	ENST00000255416.9
MYBPH	XM_047421205.1	c.1428C>T	p.Gly476=	synonymous_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPH	ENST00000255416.9	c.1305C>T	p.Gly435=	synonymous_variant	9/11	1	NM_004997.3	P1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152140 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

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: 0.0000882

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000897 AC: 225 AN: 250708 Hom.: 1 AF XY: 0.000738 AC XY: 100 AN XY: 135580

Gnomad AFR exome AF: 0.00723

Gnomad AMR exome AF: 0.000897

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: 0.0000972

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000431 AC: 630 AN: 1461458 Hom.: 2 Cov.: 33 AF XY: 0.000409 AC XY: 297 AN XY: 726944

Gnomad4 AFR exome AF: 0.00795

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.00662

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000585

Gnomad4 OTH exome AF: 0.00124

GnomAD4 genome AF: 0.00241 AC: 367 AN: 152258 Hom.: 2 Cov.: 32 AF XY: 0.00208 AC XY: 155 AN XY: 74440

Gnomad4 AFR AF: 0.00765

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.00301

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

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	-0.63
Cadd	Benign	13
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs12087754; hg19: chr1-203138146; COSMIC: COSV55143138; COSMIC: COSV55143138;