chr1-180281025-T-C

Variant names:

• chr1-180281025-T-C
• rs716760
• XM_047432084.1:c.*586A>G

Variant summary

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

The ENST00000642319.1(ACBD6):​c.*174+281A>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 152,056 control chromosomes in the GnomAD database, including 20,538 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 (20538 hom., cov: 32)
• Consequence: ACBD6 ENST00000642319.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642319.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACBD6	ENST00000642319.1		c.*174+281A>G		intron	N/A	ENSP00000495710.1	Q9BR61
	ACBD6	ENST00000496993.5	TSL:5	n.639+281A>G		intron	N/A
	ACBD6	ENST00000645415.1		n.*407+281A>G		intron	N/A	ENSP00000494507.1	A0A2R8Y544

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73908 AN: 151938 Hom.: 20538 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.486 AC: 73898 AN: 152056 Hom.: 20538 Cov.: 32 AF XY: 0.491 AC XY: 36525 AN XY: 74314

African (AFR) AF: 0.200 AC: 8314 AN: 41490

American (AMR) AF: 0.488 AC: 7460 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1836 AN: 3470

East Asian (EAS) AF: 0.576 AC: 2975 AN: 5162

South Asian (SAS) AF: 0.661 AC: 3184 AN: 4816

European-Finnish (FIN) AF: 0.631 AC: 6670 AN: 10564

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41711 AN: 67970

Other (OTH) AF: 0.489 AC: 1030 AN: 2106

Alfa AF: 0.576 Hom.: 14489

Bravo AF: 0.462

Asia WGS AF: 0.533 AC: 1851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.38
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs716760; hg19: chr1-180250160; COSMIC: COSV55374134; COSMIC: COSV55374134;