1-241887086-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130398.4(EXO1):c.2405+1579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 152,284 control chromosomes in the GnomAD database, including 68,391 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 0.95 (68391 hom., cov: 33)
• Consequence: EXO1 NM_130398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXO1	NM_130398.4	c.2405+1579T>C		intron_variant		ENST00000366548.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXO1	ENST00000366548.8	c.2405+1579T>C		intron_variant		1	NM_130398.4	P2

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144056 AN: 152166 Hom.: 68354 Cov.: 33

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.977

Gnomad OTH AF: 0.945

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

GnomAD4 genome AF: 0.947 AC: 144148 AN: 152284 Hom.: 68391 Cov.: 33 AF XY: 0.946 AC XY: 70420 AN XY: 74454

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.974

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.977

Gnomad4 OTH AF: 0.946

Alfa AF: 0.962 Hom.: 8739

Bravo AF: 0.941

Asia WGS AF: 0.919 AC: 3195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.1
Dann	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs1635484; hg19: chr1-242050388;