1-180281025-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 XM_047432084.1(ACBD6):​c.*586A>G variant causes a 3 prime UTR 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 XM_047432084.1 3_prime_UTR
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACBD6	XM_047432084.1	c.*586A>G		3_prime_UTR_variant	Exon 10 of 10		XP_047288040.1
ACBD6	XM_047432080.1	c.*174+281A>G		intron_variant	Intron 9 of 9		XP_047288036.1
ACBD6	XM_047432081.1	c.*301+281A>G		intron_variant	Intron 10 of 10		XP_047288037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACBD6	ENST00000642319.1	c.*174+281A>G		intron_variant	Intron 9 of 13			ENSP00000495710.1
ACBD6	ENST00000496993.5	n.639+281A>G		intron_variant	Intron 6 of 6	5
ACBD6	ENST00000645415.1	n.*407+281A>G		intron_variant	Intron 10 of 14			ENSP00000494507.1

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 v4.3

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;