rs2250509

Positions:

• chr1-203169842-A-G
• chr1-203169842-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004997.3(MYBPH):​c.1093+449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,186 control chromosomes in the GnomAD database, including 51,196 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51196 hom., cov: 32)
• Consequence: MYBPH NM_004997.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPH	NM_004997.3	c.1093+449T>C		intron_variant		ENST00000255416.9
MYBPH	XM_047421205.1	c.1216+449T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPH	ENST00000255416.9	c.1093+449T>C		intron_variant		1	NM_004997.3	P1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124047 AN: 152068 Hom.: 51162 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.807

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.816 AC: 124125 AN: 152186 Hom.: 51196 Cov.: 32 AF XY: 0.811 AC XY: 60355 AN XY: 74416

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.799

Alfa AF: 0.852 Hom.: 74288

Bravo AF: 0.803

Asia WGS AF: 0.652 AC: 2271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.53

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: rs2250509; hg19: chr1-203138970;