rs488846

Variant names:

• chr18-54261400-T-C
• rs488846
• ENST00000756228.1:n.198-4496T>C

Variant summary

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

The ENST00000756228.1(ENSG00000298527):​n.198-4496T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,894 control chromosomes in the GnomAD database, including 5,092 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 0.25 (5092 hom., cov: 31)
• Consequence: ENSG00000298527 ENST00000756228.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• Publications: 8 publications found

Genes affected

ENSG00000298527 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000756228.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000298527	ENST00000756228.1		n.198-4496T>C		intron	N/A
	ENSG00000277324	ENST00000756323.1		n.239-239A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38512 AN: 151776 Hom.: 5093 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.254 AC: 38519 AN: 151894 Hom.: 5092 Cov.: 31 AF XY: 0.249 AC XY: 18505 AN XY: 74240

African (AFR) AF: 0.236 AC: 9794 AN: 41436

American (AMR) AF: 0.223 AC: 3393 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1046 AN: 3470

East Asian (EAS) AF: 0.0295 AC: 152 AN: 5148

South Asian (SAS) AF: 0.249 AC: 1197 AN: 4810

European-Finnish (FIN) AF: 0.221 AC: 2339 AN: 10560

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19778 AN: 67926

Other (OTH) AF: 0.259 AC: 546 AN: 2110

Alfa AF: 0.276 Hom.: 751

Bravo AF: 0.251

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.21
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs488846; hg19: chr18-51787770;