18-50992021-T-C

Variant names:

• chr18-50992021-T-C
• rs7235543
• ENST00000590722.2:n.157+17460T>C

Variant summary

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

The ENST00000590722.2(ENSG00000267699):​n.157+17460T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 152,254 control chromosomes in the GnomAD database, including 173 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 0.032 (173 hom., cov: 32)
• Consequence: ENSG00000267699 ENST00000590722.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 2 publications found

Genes affected

ENSG00000267699 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590722.2. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000267699	ENST00000590722.2	TSL:2	n.157+17460T>C		intron	N/A	ENSP00000465737.1
	ENSG00000267699	ENST00000588256.1	TSL:4	n.334+7458T>C		intron	N/A
	ENSG00000289868	ENST00000797254.1		n.163-17510A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0315 AC: 4791 AN: 152136 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00443

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0128

Gnomad OTH AF: 0.0326

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

GnomAD4 genome AF: 0.0316 AC: 4804 AN: 152254 Hom.: 173 Cov.: 32 AF XY: 0.0310 AC XY: 2306 AN XY: 74456

African (AFR) AF: 0.0835 AC: 3466 AN: 41526

American (AMR) AF: 0.0129 AC: 198 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5184

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4830

European-Finnish (FIN) AF: 0.00443 AC: 47 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0128 AC: 870 AN: 68018

Other (OTH) AF: 0.0318 AC: 67 AN: 2110

Alfa AF: 0.0244 Hom.: 20

Bravo AF: 0.0343

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7235543; hg19: chr18-48518391;