18-59362474-C-T

Variant names:

• chr18-59362474-C-T
• rs2282583
• ENST00000591331.1:n.129+1646C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000591331.1(ENSG00000267677):​n.129+1646C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,078 control chromosomes in the GnomAD database, including 1,602 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 0.14 (1602 hom., cov: 32)
• Consequence: ENSG00000267677 ENST00000591331.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 7 publications found

Genes affected

ENSG00000267677 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000267677	ENST00000591331.1	n.129+1646C>T		intron_variant	Intron 1 of 1	2
ENSG00000267677	ENST00000767578.1	n.233-23988C>T		intron_variant	Intron 1 of 1
ENSG00000267677	ENST00000767579.1	n.842+10672C>T		intron_variant	Intron 1 of 1
ENSG00000267677	ENST00000767580.1	n.322+3398C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20759 AN: 151960 Hom.: 1596 Cov.: 32

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.137 AC: 20766 AN: 152078 Hom.: 1602 Cov.: 32 AF XY: 0.136 AC XY: 10115 AN XY: 74320

African (AFR) AF: 0.0606 AC: 2516 AN: 41512

American (AMR) AF: 0.171 AC: 2617 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.0288 AC: 149 AN: 5178

South Asian (SAS) AF: 0.147 AC: 707 AN: 4822

European-Finnish (FIN) AF: 0.166 AC: 1745 AN: 10532

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12068 AN: 67970

Other (OTH) AF: 0.130 AC: 274 AN: 2106

Alfa AF: 0.167 Hom.: 1498

Bravo AF: 0.132

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.80
PhyloP100		-0.31

Splicing

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

Other links and lift over

dbSNP: rs2282583; hg19: chr18-57029706;