NM_004997.3:c.750G>C

Variant names:

• chr1-203171426-C-G
• rs12070378
• NM_004997.3:c.750G>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004997.3(MYBPH):​c.750G>C​(p.Val250Val) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.247
• Publications: 0 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 -17 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 VariationId is 732636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.247 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.750G>C	p.Val250Val	synonymous	Exon 5 of 11	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.750G>C	p.Val250Val	synonymous	Exon 5 of 11	ENSP00000255416.4	Q13203
	MYBPH	ENST00000966288.1		c.825G>C	p.Val275Val	synonymous	Exon 5 of 10	ENSP00000636347.1
	MYBPH	ENST00000966289.1		c.825G>C	p.Val275Val	synonymous	Exon 5 of 11	ENSP00000636348.1

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

GnomAD2 exomes AF: 0.00103 AC: 259 AN: 250896 AF XY: 0.000863

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 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

African (AFR) AF: 0.00845 AC: 283 AN: 33480

American (AMR) AF: 0.00121 AC: 54 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 173 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000129 AC: 144 AN: 1111974

Other (OTH) AF: 0.00129 AC: 78 AN: 60392

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

African (AFR) AF: 0.00810 AC: 337 AN: 41580

American (AMR) AF: 0.000849 AC: 13 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68024

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.57
PhyloP100		-0.25
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs12070378; hg19: chr1-203140554;