chr18-57838630-C-A

Variant names:

• chr18-57838630-C-A
• rs576180
• ENST00000591045.1:n.155C>A

Variant summary

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

The ENST00000591045.1(RSL24D1P11):​n.155C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 557,946 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: RSL24D1P11 ENST00000591045.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55
• Publications: 1 publications found

Genes affected

RSL24D1P11 (HGNC:37881): (ribosomal L24 domain containing 1 pseudogene 11)

ENSG00000303117 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSL24D1P11		n.57838630C>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSL24D1P11	ENST00000591045.1	n.155C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000303117	ENST00000791946.1	n.354+5426C>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152048 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000986 AC: 4 AN: 405780 Hom.: 0 Cov.: 2 AF XY: 0.00000436 AC XY: 1 AN XY: 229416

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

African (AFR) AF: 0.000180 AC: 2 AN: 11122

American (AMR) AF: 0.0000281 AC: 1 AN: 35634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13212

East Asian (EAS) AF: 0.00 AC: 0 AN: 16206

South Asian (SAS) AF: 0.00 AC: 0 AN: 66026

European-Finnish (FIN) AF: 0.0000489 AC: 1 AN: 20466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 222274

Other (OTH) AF: 0.00 AC: 0 AN: 19412

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.043174), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152166 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74398

African (AFR) AF: 0.0000482 AC: 2 AN: 41490

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		3.6

Splicing

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

Other links and lift over

dbSNP: rs576180; hg19: chr18-55505862;