rs4408133

chr1-241886347-G-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+840G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,048 control chromosomes in the GnomAD database, including 6,947 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 0.29 (6947 hom., cov: 33)
• Consequence: EXO1 NM_130398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXO1	NM_130398.4	c.2405+840G>C		intron_variant		ENST00000366548.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXO1	ENST00000366548.8	c.2405+840G>C		intron_variant		1	NM_130398.4	P2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44466 AN: 151930 Hom.: 6941 Cov.: 33

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.293 AC: 44480 AN: 152048 Hom.: 6947 Cov.: 33 AF XY: 0.292 AC XY: 21715 AN XY: 74320

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.305

Alfa AF: 0.313 Hom.: 990

Bravo AF: 0.276

Asia WGS AF: 0.307 AC: 1068 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	11
Dann	Benign	0.81

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: rs4408133; hg19: chr1-242049649;