rs2067000

Variant names:

• chr5-135671865-A-C
• rs2067000
• NM_001349335.2:c.-521+36909A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-135671865-A-C
• chr5-135671865-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001349335.2(SLC25A48):​c.-521+36909A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 126,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.025 (0 hom., cov: 21)
  • Failed GnomAD Quality Control
• Consequence: SLC25A48 NM_001349335.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• Publications: 2 publications found

Genes affected

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the NFE (0.0262) population. However there is too low homozygotes in high coverage region: (expected more than 19, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349335.2. 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
	SLC25A48	NM_001349335.2		c.-521+36909A>C		intron	N/A	NP_001336264.1	J3KQI1
	SLC25A48	NM_001349345.2		c.-521+36909A>C		intron	N/A	NP_001336274.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A48	ENST00000646290.1		c.-521+36909A>C		intron	N/A	ENSP00000493514.1	J3KQI1
	SLC25A48	ENST00000647391.1		n.829+118A>C		intron	N/A
	SLC25A48	ENST00000698885.1		n.365-89159A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3171 AN: 126746 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.0223

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.00855

Gnomad MID AF: 0.00690

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0250 AC: 3174 AN: 126826 Hom.: 0 Cov.: 21 AF XY: 0.0242 AC XY: 1484 AN XY: 61328

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0265 AC: 898 AN: 33904

American (AMR) AF: 0.0213 AC: 255 AN: 11960

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 78 AN: 3014

East Asian (EAS) AF: 0.0250 AC: 90 AN: 3594

South Asian (SAS) AF: 0.0257 AC: 100 AN: 3898

European-Finnish (FIN) AF: 0.00855 AC: 72 AN: 8424

Middle Eastern (MID) AF: 0.00746 AC: 2 AN: 268

European-Non Finnish (NFE) AF: 0.0273 AC: 1619 AN: 59254

Other (OTH) AF: 0.0247 AC: 42 AN: 1702

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00420 Hom.: 14833

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.48
DANN	Benign	0.33
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs2067000; hg19: chr5-135007554;