rs2250509

Variant names:

• chr1-203169842-A-G
• rs2250509
• NM_004997.3:c.1093+449T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004997.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPH	NM_004997.3	MANE Select	c.1093+449T>C		intron	N/A	NP_004988.2	Q13203

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPH	ENST00000255416.9	TSL:1 MANE Select	c.1093+449T>C		intron	N/A	ENSP00000255416.4	Q13203
	MYBPH	ENST00000966288.1		c.1168+449T>C		intron	N/A	ENSP00000636347.1
	MYBPH	ENST00000966289.1		c.1168+449T>C		intron	N/A	ENSP00000636348.1

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

African (AFR) AF: 0.784 AC: 32526 AN: 41508

American (AMR) AF: 0.749 AC: 11453 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2770 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2241 AN: 5158

South Asian (SAS) AF: 0.830 AC: 3993 AN: 4808

European-Finnish (FIN) AF: 0.853 AC: 9051 AN: 10606

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59318 AN: 68020

Other (OTH) AF: 0.799 AC: 1689 AN: 2114

Alfa AF: 0.843 Hom.: 105218

Bravo AF: 0.803

Asia WGS AF: 0.652 AC: 2271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.53
PhyloP100		0.052
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2250509; hg19: chr1-203138970;