NM_002465.4:c.26-57delG

Variant names:

• chr12-101614438-AG-A
• rs111379309
• NM_002465.4:c.26-57delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002465.4(MYBPC1):​c.26-57delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,601,492 control chromosomes in the GnomAD database, including 1,305 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (644 hom., cov: 32)
  • Exomes 𝑓: 0.014 (661 hom.)
• Consequence: MYBPC1 NM_002465.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17
• Publications: 1 publications found

Genes affected

MYBPC1 (HGNC:7549): (myosin binding protein C1) This gene encodes a member of the myosin-binding protein C family. Myosin-binding protein C family members are myosin-associated proteins found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The encoded protein is the slow skeletal muscle isoform of myosin-binding protein C and plays an important role in muscle contraction by recruiting muscle-type creatine kinase to myosin filaments. Mutations in this gene are associated with distal arthrogryposis type I. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

MYBPC1 Gene-Disease associations (from GenCC):

• arthrogryposis, distal, type 1B

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• myopathy, congenital, with tremor

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• lethal congenital contracture syndrome 4

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• digitotalar dysmorphism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• lethal congenital contracture syndrome 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC105369938 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-101614438-AG-A is Benign according to our data. Variant chr12-101614438-AG-A is described in ClinVar as Benign. ClinVar VariationId is 1278156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002465.4. 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
	MYBPC1	NM_002465.4	MANE Select	c.26-57delG		intron	N/A	NP_002456.2
	MYBPC1	NM_001404675.1		c.26-57delG		intron	N/A	NP_001391604.1
	MYBPC1	NM_001254718.3		c.26-57delG		intron	N/A	NP_001241647.1	Q00872-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC1	ENST00000361466.7	TSL:1 MANE Select	c.26-57delG		intron	N/A	ENSP00000354849.2	Q00872-4
	MYBPC1	ENST00000361685.6	TSL:1	c.26-57delG		intron	N/A	ENSP00000354845.2	Q00872-2
	MYBPC1	ENST00000545503.6	TSL:1	c.26-57delG		intron	N/A	ENSP00000440034.2	Q00872-10

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8557 AN: 152128 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.0137 AC: 19837 AN: 1449246 Hom.: 661 AF XY: 0.0131 AC XY: 9428 AN XY: 721588

African (AFR) AF: 0.174 AC: 5783 AN: 33208

American (AMR) AF: 0.0174 AC: 774 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.00480 AC: 125 AN: 26026

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39530

South Asian (SAS) AF: 0.00764 AC: 654 AN: 85628

European-Finnish (FIN) AF: 0.00234 AC: 124 AN: 53100

Middle Eastern (MID) AF: 0.0285 AC: 163 AN: 5716

European-Non Finnish (NFE) AF: 0.0100 AC: 11019 AN: 1101738

Other (OTH) AF: 0.0199 AC: 1193 AN: 59900

GnomAD4 genome AF: 0.0563 AC: 8572 AN: 152246 Hom.: 644 Cov.: 32 AF XY: 0.0544 AC XY: 4048 AN XY: 74450

African (AFR) AF: 0.172 AC: 7150 AN: 41508

American (AMR) AF: 0.0322 AC: 493 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4822

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 697 AN: 68026

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.00366 Hom.: 4

Bravo AF: 0.0642

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
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: rs111379309; hg19: chr12-102008216;