rs1418761

Variant names:

• chr1-241879584-G-A
• rs1418761
• NM_130398.4:c.2109+241G>A

Variant summary

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

The NM_130398.4(EXO1):​c.2109+241G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,300 control chromosomes in the GnomAD database, including 68,085 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 0.94 (68085 hom., cov: 33)
• Consequence: EXO1 NM_130398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• 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=-0.86).
• 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 rank	MANE	Protein	UniProt
EXO1	NM_130398.4	c.2109+241G>A		intron_variant	Intron 13 of 15	ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.2109+241G>A		intron_variant	Intron 13 of 15	1	NM_130398.4	ENSP00000355506.3
EXO1	ENST00000348581.9	c.2109+241G>A		intron_variant	Intron 11 of 13	1		ENSP00000311873.5
EXO1	ENST00000518483.5	c.2109+241G>A		intron_variant	Intron 11 of 13	1		ENSP00000430251.1
EXO1	ENST00000521202.2	c.303+241G>A		intron_variant	Intron 1 of 2	5		ENSP00000428326.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143733 AN: 152182 Hom.: 68051 Cov.: 33

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.944

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

GnomAD4 genome AF: 0.944 AC: 143821 AN: 152300 Hom.: 68085 Cov.: 33 AF XY: 0.943 AC XY: 70248 AN XY: 74456

African (AFR) AF: 0.880 AC: 36544 AN: 41544

American (AMR) AF: 0.974 AC: 14881 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3272 AN: 3472

East Asian (EAS) AF: 0.871 AC: 4519 AN: 5188

South Asian (SAS) AF: 0.936 AC: 4516 AN: 4826

European-Finnish (FIN) AF: 0.994 AC: 10557 AN: 10620

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.976 AC: 66415 AN: 68044

Other (OTH) AF: 0.945 AC: 1997 AN: 2114

Alfa AF: 0.958 Hom.: 10305

Bravo AF: 0.938

Asia WGS AF: 0.916 AC: 3186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.37
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: rs1418761; hg19: chr1-242042886;