chr19-6182745-A-C

Position:

• chr19-6182745-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_030924.5(ACSBG2):​c.907-6A>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,613,648 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (26 hom., cov: 31)
  • Exomes 𝑓: 0.00098 (19 hom.)
• Consequence: ACSBG2 NM_030924.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001266
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

Genes affected

ACSBG2 (HGNC:24174): (acyl-CoA synthetase bubblegum family member 2) Enables acyl-CoA hydrolase activity and arachidonate-CoA ligase activity. Acts upstream of or within fatty acid metabolic process. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

LOC105372255 (HGNC:):

RFX2 (HGNC:9983): (regulatory factor X2) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X3, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. This protein can bind to cis elements in the promoter of the IL-5 receptor alpha gene. Two transcript variants encoding different isoforms have been described for this gene, and both variants utilize alternative polyadenylation sites. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 19-6182745-A-C is Benign according to our data. Variant chr19-6182745-A-C is described in ClinVar as [Benign]. Clinvar id is 714755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00913 (1391/152282) while in subpopulation AFR AF= 0.0319 (1327/41538). AF 95% confidence interval is 0.0305. There are 26 homozygotes in gnomad4. There are 637 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSBG2	NM_030924.5	c.907-6A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000588485.6
LOC105372255	XR_936282.3	n.50-6302T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSBG2	ENST00000588485.6	c.907-6A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_030924.5	P1

Frequencies

GnomAD3 genomes AF: 0.00906 AC: 1379 AN: 152164 Hom.: 26 Cov.: 31

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00245 AC: 614 AN: 250746 Hom.: 14 AF XY: 0.00191 AC XY: 259 AN XY: 135536

Gnomad AFR exome AF: 0.0324

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.000979 AC: 1431 AN: 1461366 Hom.: 19 Cov.: 32 AF XY: 0.000869 AC XY: 632 AN XY: 726984

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.00228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000522

Gnomad4 OTH exome AF: 0.00253

GnomAD4 genome AF: 0.00913 AC: 1391 AN: 152282 Hom.: 26 Cov.: 31 AF XY: 0.00855 AC XY: 637 AN XY: 74468

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00495 Hom.: 4

Bravo AF: 0.0101

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.076
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0040
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

Publications

LitVar

Other links and lift over

dbSNP: rs113123404; hg19: chr19-6182756;