rs11711441

Variant names:

• chr3-183103487-G-A
• rs11711441
• ENST00000492597.5:c.-101-8882C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000492597.5(MCCC1):​c.-101-8882C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,898 control chromosomes in the GnomAD database, including 1,219 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 0.12 (1219 hom., cov: 30)
• Consequence: MCCC1 ENST00000492597.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 46 publications found

Genes affected

MCCC1 (HGNC:6936): (methylcrotonyl-CoA carboxylase subunit 1) This gene encodes the large subunit of 3-methylcrotonyl-CoA carboxylase. This enzyme functions as a heterodimer and catalyzes the carboxylation of 3-methylcrotonyl-CoA to form 3-methylglutaconyl-CoA. Mutations in this gene are associated with 3-Methylcrotonylglycinuria, an autosomal recessive disorder of leucine catabolism. [provided by RefSeq, Jul 2008]

MCCC1 Gene-Disease associations (from GenCC):

• 3-methylcrotonyl-CoA carboxylase 1 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 3-methylcrotonyl-CoA carboxylase deficiency

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000492597.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCCC1	ENST00000492597.5	TSL:1	c.-101-8882C>T		intron	N/A	ENSP00000419898.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18252 AN: 151782 Hom.: 1218 Cov.: 30

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.120 AC: 18254 AN: 151898 Hom.: 1219 Cov.: 30 AF XY: 0.119 AC XY: 8860 AN XY: 74266

African (AFR) AF: 0.0751 AC: 3115 AN: 41452

American (AMR) AF: 0.105 AC: 1599 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1055 AN: 5152

South Asian (SAS) AF: 0.159 AC: 766 AN: 4806

European-Finnish (FIN) AF: 0.118 AC: 1247 AN: 10548

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9698 AN: 67900

Other (OTH) AF: 0.126 AC: 265 AN: 2104

Alfa AF: 0.144 Hom.: 3813

Bravo AF: 0.117

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.93
DANN	Benign	0.55
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11711441; hg19: chr3-182821275;