rs4150027

Variant names:

• chr1-241890536-T-C
• rs4150027
• ENST00000518741.1:n.152-1988T>C

Variant summary

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

The ENST00000518741.1(EXO1):​n.152-1988T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,046 control chromosomes in the GnomAD database, including 4,258 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 0.23 (4258 hom., cov: 33)
• Consequence: EXO1 ENST00000518741.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 3 publications found

Genes affected

EXO1 (HGNC:3511): (exonuclease 1) This gene encodes a protein with 5' to 3' exonuclease activity as well as an RNase H activity. It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in mismatch repair and recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms. [provided by RefSeq, Jul 2008]

EXO1 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 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
EXO1	ENST00000518741.1	n.152-1988T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34646 AN: 151928 Hom.: 4257 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.228 AC: 34659 AN: 152046 Hom.: 4258 Cov.: 33 AF XY: 0.225 AC XY: 16725 AN XY: 74332

African (AFR) AF: 0.201 AC: 8322 AN: 41492

American (AMR) AF: 0.193 AC: 2940 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3470

East Asian (EAS) AF: 0.0170 AC: 88 AN: 5168

South Asian (SAS) AF: 0.211 AC: 1017 AN: 4826

European-Finnish (FIN) AF: 0.236 AC: 2489 AN: 10558

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17815 AN: 67952

Other (OTH) AF: 0.238 AC: 504 AN: 2114

Alfa AF: 0.236 Hom.: 552

Bravo AF: 0.223

Asia WGS AF: 0.133 AC: 462 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.45
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs4150027; hg19: chr1-242053838;