rs6700986

Variant names:

• chr1-180452403-G-A
• rs6700986
• NM_032360.4:c.385-22141C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032360.4(ACBD6):​c.385-22141C>T 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 151,796 control chromosomes in the GnomAD database, including 20,774 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 (20774 hom., cov: 30)
• Consequence: ACBD6 NM_032360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACBD6	NM_032360.4	c.385-22141C>T		intron_variant	Intron 3 of 7	ENST00000367595.4	NP_115736.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACBD6	ENST00000367595.4	c.385-22141C>T		intron_variant	Intron 3 of 7	1	NM_032360.4	ENSP00000356567.3
ACBD6	ENST00000642319.1	c.385-22141C>T		intron_variant	Intron 3 of 13			ENSP00000495710.1
ACBD6	ENST00000645415.1	n.385-22141C>T		intron_variant	Intron 3 of 14			ENSP00000494507.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73824 AN: 151678 Hom.: 20774 Cov.: 30

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.486 AC: 73813 AN: 151796 Hom.: 20774 Cov.: 30 AF XY: 0.492 AC XY: 36523 AN XY: 74164

African (AFR) AF: 0.187 AC: 7723 AN: 41392

American (AMR) AF: 0.486 AC: 7411 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1837 AN: 3464

East Asian (EAS) AF: 0.563 AC: 2903 AN: 5156

South Asian (SAS) AF: 0.660 AC: 3171 AN: 4804

European-Finnish (FIN) AF: 0.654 AC: 6872 AN: 10514

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42146 AN: 67920

Other (OTH) AF: 0.486 AC: 1021 AN: 2102

Alfa AF: 0.524 Hom.: 2951

Bravo AF: 0.460

Asia WGS AF: 0.528 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.56
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6700986; hg19: chr1-180421538;