rs2291447

Variant names:

• chr17-45135596-G-T
• rs2291447
• ENST00000591859.5:c.-153+4G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-45135596-G-T
• chr17-45135596-G-A
• chr17-45135596-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_001378112.1(ACBD4):​c.-700G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 154,056 control chromosomes in the GnomAD database, including 16,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.46 (16499 hom., cov: 34)
  • Exomes 𝑓: 0.44 (234 hom.)
• Consequence: ACBD4 NM_001378112.1 5_prime_UTR_premature_start_codon_gain
• Scores: Splicing: ADA: 0.9739
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 21 publications found

Genes affected

ACBD4 (HGNC:23337): (acyl-CoA binding domain containing 4) This gene encodes a member of the acyl-coenzyme A binding domain containing protein family. All family members contain the conserved acyl-Coenzyme A binding domain, which binds acyl-CoA thiol esters. They are thought to play roles in acyl-CoA dependent lipid metabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378112.1. 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
	ACBD4	NM_001378112.1		c.-700G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001365041.1
	ACBD4	NM_001378112.1		c.-700G>T		5_prime_UTR	Exon 2 of 10	NP_001365041.1
	ACBD4	NM_001321352.2		c.-153+4G>T		splice_region intron	N/A	NP_001308281.1	A0A0S2Z5Y4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACBD4	ENST00000591859.5	TSL:1	c.-153+4G>T		splice_region intron	N/A	ENSP00000465610.1	Q8NC06-3
	ACBD4	ENST00000431281.5	TSL:5	c.-150G>T		splice_region	Exon 2 of 12	ENSP00000405969.1	Q8NC06-3
	ACBD4	ENST00000865137.1		c.-150G>T		splice_region	Exon 1 of 11	ENSP00000535196.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70099 AN: 152038 Hom.: 16491 Cov.: 34

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.442 AC: 839 AN: 1900 Hom.: 234 Cov.: 0 AF XY: 0.474 AC XY: 539 AN XY: 1138

African (AFR) AF: 0.500 AC: 5 AN: 10

American (AMR) AF: 0.266 AC: 73 AN: 274

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 3 AN: 6

East Asian (EAS) AF: 0.111 AC: 6 AN: 54

South Asian (SAS) AF: 0.552 AC: 233 AN: 422

European-Finnish (FIN) AF: 0.294 AC: 10 AN: 34

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.460 AC: 483 AN: 1050

Other (OTH) AF: 0.520 AC: 26 AN: 50

GnomAD4 genome AF: 0.461 AC: 70130 AN: 152156 Hom.: 16499 Cov.: 34 AF XY: 0.457 AC XY: 33994 AN XY: 74388

African (AFR) AF: 0.442 AC: 18334 AN: 41488

American (AMR) AF: 0.402 AC: 6153 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1294 AN: 5176

South Asian (SAS) AF: 0.541 AC: 2607 AN: 4818

European-Finnish (FIN) AF: 0.415 AC: 4403 AN: 10608

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34261 AN: 67988

Other (OTH) AF: 0.451 AC: 952 AN: 2110

Alfa AF: 0.486 Hom.: 65140

Bravo AF: 0.457

Asia WGS AF: 0.381 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.69
PhyloP100		-0.41
PromoterAI		0.018	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Pathogenic	0.81

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2291447;

hg19: chr17-43212963;