rs2642531

Variant names:

• chr1-203174597-G-C
• rs2642531
• NM_004997.3:c.341C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-203174597-G-C
• chr1-203174597-G-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.341C>G​(p.Ala114Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,594,978 control chromosomes in the GnomAD database, including 24,005 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (6106 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17899 hom.)
• Consequence: MYBPH NM_004997.3 missense, splice_region
• Scores: Splicing: ADA: 0.0005832
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 16 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 (MetaRNN=2.9930472E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYBPH	NM_004997.3	c.341C>G	p.Ala114Gly	missense_variant, splice_region_variant	Exon 3 of 11	ENST00000255416.9	NP_004988.2
MYBPH	XM_047421205.1	c.464C>G	p.Ala155Gly	missense_variant, splice_region_variant	Exon 4 of 12		XP_047277161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYBPH	ENST00000255416.9	c.341C>G	p.Ala114Gly	missense_variant, splice_region_variant	Exon 3 of 11	1	NM_004997.3	ENSP00000255416.4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36050 AN: 152028 Hom.: 6093 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.171 AC: 41278 AN: 241992 AF XY: 0.160

Gnomad AFR exome AF: 0.496

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.149

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.142 AC: 205586 AN: 1442832 Hom.: 17899 Cov.: 32 AF XY: 0.140 AC XY: 100354 AN XY: 714630

African (AFR) AF: 0.508 AC: 16825 AN: 33126

American (AMR) AF: 0.239 AC: 10457 AN: 43830

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5057 AN: 25798

East Asian (EAS) AF: 0.175 AC: 6865 AN: 39152

South Asian (SAS) AF: 0.128 AC: 10888 AN: 85326

European-Finnish (FIN) AF: 0.116 AC: 6149 AN: 53002

Middle Eastern (MID) AF: 0.199 AC: 1128 AN: 5676

European-Non Finnish (NFE) AF: 0.126 AC: 138099 AN: 1097592

Other (OTH) AF: 0.171 AC: 10118 AN: 59330

GnomAD4 genome AF: 0.237 AC: 36102 AN: 152146 Hom.: 6106 Cov.: 32 AF XY: 0.234 AC XY: 17434 AN XY: 74396

African (AFR) AF: 0.478 AC: 19816 AN: 41444

American (AMR) AF: 0.256 AC: 3916 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 692 AN: 3466

East Asian (EAS) AF: 0.148 AC: 769 AN: 5180

South Asian (SAS) AF: 0.125 AC: 605 AN: 4828

European-Finnish (FIN) AF: 0.113 AC: 1195 AN: 10610

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8538 AN: 68008

Other (OTH) AF: 0.220 AC: 466 AN: 2114

Alfa AF: 0.149 Hom.: 1591

Bravo AF: 0.262

TwinsUK AF: 0.126 AC: 467

ALSPAC AF: 0.139 AC: 534

ESP6500AA AF: 0.486 AC: 2143

ESP6500EA AF: 0.131 AC: 1124

ExAC AF: 0.170 AC: 20623

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.13	T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.00030	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	.;L
PhyloP100		1.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	.;N
REVEL	Benign	0.072
Sift	Benign	0.082	.;T
Sift4G	Uncertain	0.029	D;D
Polyphen		0.048	.;B
Vest4		0.053
MPC		0.14
ClinPred		0.020	T
GERP RS		4.6
Varity_R		0.13
gMVP		0.22
Mutation Taster		=70/30	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00058
dbscSNV1_RF	Benign	0.042
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: rs2642531; hg19: chr1-203143725; COSMIC: COSV55138164; COSMIC: COSV55138164;