1-241877473-C-T

Variant names:

• chr1-241877473-C-T
• rs1635501
• NM_130398.4:c.1515-1276C>T

Variant summary

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

The NM_130398.4(EXO1):​c.1515-1276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,858 control chromosomes in the GnomAD database, including 22,658 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 0.54 (22658 hom., cov: 31)
• Consequence: EXO1 NM_130398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 31 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXO1	NM_130398.4	c.1515-1276C>T		intron_variant	Intron 12 of 15	ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.1515-1276C>T		intron_variant	Intron 12 of 15	1	NM_130398.4	ENSP00000355506.3
EXO1	ENST00000348581.9	c.1515-1276C>T		intron_variant	Intron 10 of 13	1		ENSP00000311873.5
EXO1	ENST00000518483.5	c.1515-1276C>T		intron_variant	Intron 10 of 13	1		ENSP00000430251.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82042 AN: 151740 Hom.: 22623 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.541 AC: 82135 AN: 151858 Hom.: 22658 Cov.: 31 AF XY: 0.547 AC XY: 40574 AN XY: 74236

African (AFR) AF: 0.484 AC: 20048 AN: 41386

American (AMR) AF: 0.646 AC: 9851 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1441 AN: 3466

East Asian (EAS) AF: 0.796 AC: 4118 AN: 5174

South Asian (SAS) AF: 0.552 AC: 2655 AN: 4812

European-Finnish (FIN) AF: 0.564 AC: 5941 AN: 10532

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.535 AC: 36350 AN: 67924

Other (OTH) AF: 0.558 AC: 1178 AN: 2110

Alfa AF: 0.539 Hom.: 64596

Bravo AF: 0.545

Asia WGS AF: 0.655 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.64
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1635501; hg19: chr1-242040775;