rs526593

Variant names:

• chr1-194128586-A-T
• rs526593
• ENST00000655677.1:n.46+2401A>T

Variant summary

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

The ENST00000655677.1(ENSG00000227240):​n.46+2401A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,986 control chromosomes in the GnomAD database, including 12,732 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 0.32 (12732 hom., cov: 33)
• Consequence: ENSG00000227240 ENST00000655677.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• Publications: 2 publications found

Genes affected

ENSG00000227240 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000655677.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000227240	ENST00000655677.1		n.46+2401A>T		intron	N/A
	ENSG00000227240	ENST00000656143.2		n.379-68937A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48104 AN: 151868 Hom.: 12690 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.317 AC: 48213 AN: 151986 Hom.: 12732 Cov.: 33 AF XY: 0.314 AC XY: 23336 AN XY: 74298

African (AFR) AF: 0.729 AC: 30249 AN: 41476

American (AMR) AF: 0.182 AC: 2780 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3466

East Asian (EAS) AF: 0.144 AC: 745 AN: 5178

South Asian (SAS) AF: 0.224 AC: 1082 AN: 4824

European-Finnish (FIN) AF: 0.192 AC: 2038 AN: 10588

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9888 AN: 67852

Other (OTH) AF: 0.261 AC: 551 AN: 2108

Alfa AF: 0.254 Hom.: 1061

Bravo AF: 0.332

Asia WGS AF: 0.209 AC: 728 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		-0.39

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs526593;

hg19: chr1-194097716;

COSMIC: COSV60006795;