18-22504711-T-G

Variant names:

• chr18-22504711-T-G
• rs473518
• ENST00000731115.1:n.258-28345A>C

Variant summary

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

The ENST00000731115.1(ENSG00000289624):​n.258-28345A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,112 control chromosomes in the GnomAD database, including 51,578 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 0.82 (51578 hom., cov: 31)
• Consequence: ENSG00000289624 ENST00000731115.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 6 publications found

Genes affected

ENSG00000289624 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.843 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
ENSG00000289624	ENST00000731115.1	n.258-28345A>C		intron_variant	Intron 1 of 1
ENSG00000295614	ENST00000731317.1	n.152+1518T>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125000 AN: 151994 Hom.: 51540 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.822 AC: 125091 AN: 152112 Hom.: 51578 Cov.: 31 AF XY: 0.823 AC XY: 61219 AN XY: 74358

African (AFR) AF: 0.816 AC: 33878 AN: 41504

American (AMR) AF: 0.728 AC: 11117 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2876 AN: 3472

East Asian (EAS) AF: 0.759 AC: 3916 AN: 5158

South Asian (SAS) AF: 0.865 AC: 4169 AN: 4820

European-Finnish (FIN) AF: 0.837 AC: 8857 AN: 10576

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57445 AN: 67990

Other (OTH) AF: 0.831 AC: 1756 AN: 2114

Alfa AF: 0.836 Hom.: 14742

Bravo AF: 0.812

Asia WGS AF: 0.770 AC: 2678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.86
DANN	Benign	0.49
PhyloP100		-0.58

Splicing

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

Other links and lift over

dbSNP: rs473518; hg19: chr18-20084674;