rs11711441

Positions:

• chr3-183103487-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCCC1	XM_047448586.1	c.39-8882C>T		intron_variant
MCCC1	XM_047448591.1	c.39-8882C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCCC1	ENST00000492597.5	c.-101-8882C>T		intron_variant		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

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.126

Alfa AF: 0.142 Hom.: 1037

Bravo AF: 0.117

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.93
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11711441; hg19: chr3-182821275;