1-180393392-T-C

Variant names:

• chr1-180393392-T-C
• rs10494527
• NM_032360.4:c.663+4124A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032360.4(ACBD6):​c.663+4124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,064 control chromosomes in the GnomAD database, including 20,777 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 0.49 (20777 hom., cov: 32)
• Consequence: ACBD6 NM_032360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 1 publications found

Genes affected

ACBD6 (HGNC:23339): (acyl-CoA binding domain containing 6) Predicted to enable fatty-acyl-CoA binding activity and lipid binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACBD6 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with progressive movement abnormalities

  Inheritance: AR Classification: STRONG Submitted by: G2P
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032360.4. 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
	ACBD6	NM_032360.4	MANE Select	c.663+4124A>G		intron	N/A	NP_115736.1	Q9BR61

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACBD6	ENST00000367595.4	TSL:1 MANE Select	c.663+4124A>G		intron	N/A	ENSP00000356567.3	Q9BR61
	ACBD6	ENST00000937021.1		c.777+4124A>G		intron	N/A	ENSP00000607080.1
	ACBD6	ENST00000880422.1		c.732+4124A>G		intron	N/A	ENSP00000550481.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73896 AN: 151946 Hom.: 20777 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.486 AC: 73885 AN: 152064 Hom.: 20777 Cov.: 32 AF XY: 0.492 AC XY: 36563 AN XY: 74308

African (AFR) AF: 0.187 AC: 7744 AN: 41518

American (AMR) AF: 0.487 AC: 7434 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1835 AN: 3466

East Asian (EAS) AF: 0.564 AC: 2912 AN: 5166

South Asian (SAS) AF: 0.661 AC: 3184 AN: 4820

European-Finnish (FIN) AF: 0.651 AC: 6863 AN: 10536

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42158 AN: 67962

Other (OTH) AF: 0.486 AC: 1026 AN: 2110

Alfa AF: 0.531 Hom.: 7270

Bravo AF: 0.460

Asia WGS AF: 0.529 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		1.5

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs10494527; hg19: chr1-180362527; COSMIC: COSV62572595;