rs886046776

Variant names:

• chr10-123008991-G-A
• rs886046776
• ENST00000908750.1:c.-39G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000368869.8(ACADSB):​c.-240G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000502 in 1,393,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ACADSB ENST00000368869.8 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.919
• Publications: 0 publications found

Genes affected

ACADSB (HGNC:91): (acyl-CoA dehydrogenase short/branched chain) Short/branched chain acyl-CoA dehydrogenase(ACADSB) is a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. Substrate specificity is the primary characteristic used to define members of this gene family. The ACADSB gene product has the greatest activity towards the short branched chain acyl-CoA derivative, (S)-2-methylbutyryl-CoA, but also reacts significantly with other 2-methyl branched chain substrates and with short straight chain acyl-CoAs. The cDNA encodes for a mitochondrial precursor protein which is cleaved upon mitochondrial import and predicted to yield a mature peptide of approximately 43.7-KDa. [provided by RefSeq, Jul 2008]

IKZF5 (HGNC:14283): (IKAROS family zinc finger 5) Members of the Ikaros (ZNFN1A1; MIM 603023) family of transcription factors, which includes Pegasus, are expressed in lymphocytes and are implicated in the control of lymphoid development.[supplied by OMIM, Jul 2002]

IKZF5 Gene-Disease associations (from GenCC):

• thrombocytopenia 7

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• autosomal thrombocytopenia with normal platelets

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368869.8. 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
	ACADSB	NM_001609.4	MANE Select	c.-39G>A		upstream_gene	N/A	NP_001600.1	P45954-1
	IKZF5	NM_001372123.1	MANE Select	c.-495C>T		upstream_gene	N/A	NP_001359052.1	Q9H5V7
	IKZF5	NM_001372125.1		c.-482C>T		upstream_gene	N/A	NP_001359054.1	Q9H5V7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADSB	ENST00000908750.1		c.-39G>A		5_prime_UTR	Exon 1 of 10	ENSP00000578809.1
	ACADSB	ENST00000368869.8	TSL:2	c.-240G>A		5_prime_UTR	Exon 1 of 10	ENSP00000357862.4	P45954-2
	ACADSB	ENST00000358776.7	TSL:1 MANE Select	c.-39G>A		upstream_gene	N/A	ENSP00000357873.3	P45954-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000407 AC: 6 AN: 147596 AF XY: 0.0000382

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000243

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000502 AC: 7 AN: 1393928 Hom.: 0 Cov.: 30 AF XY: 0.00000582 AC XY: 4 AN XY: 687764

African (AFR) AF: 0.00 AC: 0 AN: 31564

American (AMR) AF: 0.000196 AC: 7 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.00 AC: 0 AN: 79162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4852

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078354

Other (OTH) AF: 0.00 AC: 0 AN: 57844

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Deficiency of 2-methylbutyryl-CoA dehydrogenase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		-0.92
PromoterAI		-0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs886046776; hg19: chr10-124768507;