rs802036

Positions:

• chr7-87348578-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021151.4(CROT):​c.-21-470T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,238 control chromosomes in the GnomAD database, including 1,925 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 0.13 (1925 hom., cov: 32)
• Consequence: CROT NM_021151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330

Genes affected

CROT (HGNC:2366): (carnitine O-octanoyltransferase) This gene encodes a member of the carnitine/choline acetyltransferase family. The encoded protein converts 4,8-dimethylnonanoyl-CoA to its corresponding carnitine ester. This transesterification occurs in the peroxisome and is necessary for transport of medium- and long- chain acyl-CoA molecules out of the peroxisome to the cytosol and mitochondria. The protein thus plays a role in lipid metabolism and fatty acid beta-oxidation. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CROT	NM_021151.4	c.-21-470T>C		intron_variant		ENST00000331536.8	NP_066974.2
CROT	NM_001143935.2	c.-21-470T>C		intron_variant			NP_001137407.1
CROT	NM_001243745.3	c.-21-470T>C		intron_variant			NP_001230674.1
CROT	XM_011516337.4	c.-21-470T>C		intron_variant			XP_011514639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CROT	ENST00000331536.8	c.-21-470T>C		intron_variant		1	NM_021151.4	ENSP00000331981	P1
CROT	ENST00000412227.6	c.-21-470T>C		intron_variant		1		ENSP00000404867
CROT	ENST00000419147.6	c.-21-470T>C		intron_variant		2		ENSP00000413575
CROT	ENST00000442291.1	c.-21-470T>C		intron_variant		5		ENSP00000411983

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19034 AN: 152120 Hom.: 1910 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.000768

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0718

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.125 AC: 19087 AN: 152238 Hom.: 1925 Cov.: 32 AF XY: 0.123 AC XY: 9128 AN XY: 74432

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.0696

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0288

Gnomad4 FIN AF: 0.0888

Gnomad4 NFE AF: 0.0718

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0766 Hom.: 810

Bravo AF: 0.131

Asia WGS AF: 0.0400 AC: 139 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs802036; hg19: chr7-86977894;