rs76637913

Variant names:

• chrX-153743516-C-T
• rs76637913
• NM_000033.4:c.2019C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-153743516-C-T
• chrX-153743516-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000033.4(ABCD1):​c.2019C>T​(p.Phe673Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,203,251 control chromosomes in the GnomAD database, including 108 homozygotes. There are 5,625 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (12 hom., 412 hem., cov: 24)
  • Exomes 𝑓: 0.015 (96 hom. 5213 hem.)
• Consequence: ABCD1 NM_000033.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.765
• Publications: 3 publications found

Genes affected

ABCD1 (HGNC:61): (ATP binding cassette subfamily D member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. This peroxisomal membrane protein is likely involved in the peroxisomal transport or catabolism of very long chain fatty acids. Defects in this gene have been identified as the underlying cause of adrenoleukodystrophy, an X-chromosome recessively inherited demyelinating disorder of the nervous system. [provided by RefSeq, Jul 2008]

PLXNB3-AS1 (HGNC:40454): (PLXNB3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-153743516-C-T is Benign according to our data. Variant chrX-153743516-C-T is described in ClinVar as Benign. ClinVar VariationId is 166627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.765 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0123 (1381/112452) while in subpopulation NFE AF = 0.0174 (926/53075). AF 95% confidence interval is 0.0165. There are 12 homozygotes in GnomAd4. There are 412 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1381 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000033.4. 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
	ABCD1	NM_000033.4	MANE Select	c.2019C>T	p.Phe673Phe	synonymous	Exon 10 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.2319C>T	p.Phe773Phe	synonymous	Exon 11 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-4938G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.2019C>T	p.Phe673Phe	synonymous	Exon 10 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.2319C>T	p.Phe773Phe	synonymous	Exon 11 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2289C>T	p.Phe763Phe	synonymous	Exon 11 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1385 AN: 112398 Hom.: 12 Cov.: 24

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00878

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.000563

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.00757

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0119 AC: 1993 AN: 167711 AF XY: 0.0117

Gnomad AFR exome AF: 0.00293

Gnomad AMR exome AF: 0.00773

Gnomad ASJ exome AF: 0.0326

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00790

Gnomad NFE exome AF: 0.0165

Gnomad OTH exome AF: 0.0150

GnomAD4 exome AF: 0.0147 AC: 16030 AN: 1090799 Hom.: 96 Cov.: 37 AF XY: 0.0146 AC XY: 5213 AN XY: 358147

African (AFR) AF: 0.00225 AC: 59 AN: 26277

American (AMR) AF: 0.00709 AC: 246 AN: 34700

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 553 AN: 19229

East Asian (EAS) AF: 0.00 AC: 0 AN: 30041

South Asian (SAS) AF: 0.00835 AC: 443 AN: 53060

European-Finnish (FIN) AF: 0.00728 AC: 291 AN: 39977

Middle Eastern (MID) AF: 0.0246 AC: 71 AN: 2889

European-Non Finnish (NFE) AF: 0.0163 AC: 13707 AN: 838865

Other (OTH) AF: 0.0144 AC: 660 AN: 45761

GnomAD4 genome AF: 0.0123 AC: 1381 AN: 112452 Hom.: 12 Cov.: 24 AF XY: 0.0119 AC XY: 412 AN XY: 34634

African (AFR) AF: 0.00261 AC: 81 AN: 31067

American (AMR) AF: 0.0162 AC: 174 AN: 10724

Ashkenazi Jewish (ASJ) AF: 0.0306 AC: 81 AN: 2651

East Asian (EAS) AF: 0.000565 AC: 2 AN: 3542

South Asian (SAS) AF: 0.0138 AC: 38 AN: 2760

European-Finnish (FIN) AF: 0.00757 AC: 47 AN: 6211

Middle Eastern (MID) AF: 0.0138 AC: 3 AN: 218

European-Non Finnish (NFE) AF: 0.0174 AC: 926 AN: 53075

Other (OTH) AF: 0.0151 AC: 23 AN: 1521

Alfa AF: 0.0169 Hom.: 120

Bravo AF: 0.0117

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	4	Adrenoleukodystrophy (4)
-	-	3	not specified (3)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.1
DANN	Benign	0.92
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs76637913; hg19: chrX-153008970;