1-241889740-A-G

Variant names:

• chr1-241889740-A-G
• rs851797
• NM_130398.4:c.*140A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_130398.4(EXO1):​c.*140A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 809,600 control chromosomes in the GnomAD database, including 241,733 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 0.72 (40294 hom., cov: 33)
  • Exomes 𝑓: 0.78 (201439 hom.)
• Consequence: EXO1 NM_130398.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 14 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130398.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXO1	NM_130398.4	MANE Select	c.*140A>G		3_prime_UTR	Exon 16 of 16	NP_569082.2
	EXO1	NM_006027.4		c.*140A>G		3_prime_UTR	Exon 14 of 14	NP_006018.4
	EXO1	NM_001319224.2		c.*140A>G		3_prime_UTR	Exon 15 of 15	NP_001306153.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXO1	ENST00000366548.8	TSL:1 MANE Select	c.*140A>G		3_prime_UTR	Exon 16 of 16	ENSP00000355506.3
	EXO1	ENST00000348581.9	TSL:1	c.*140A>G		3_prime_UTR	Exon 14 of 14	ENSP00000311873.5
	EXO1	ENST00000518483.5	TSL:1	c.*267A>G		3_prime_UTR	Exon 14 of 14	ENSP00000430251.1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108921 AN: 152084 Hom.: 40281 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.722

GnomAD4 exome AF: 0.777 AC: 510749 AN: 657398 Hom.: 201439 Cov.: 8 AF XY: 0.781 AC XY: 274210 AN XY: 351108

African (AFR) AF: 0.568 AC: 9356 AN: 16458

American (AMR) AF: 0.606 AC: 21365 AN: 35252

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 16541 AN: 20182

East Asian (EAS) AF: 0.457 AC: 15029 AN: 32916

South Asian (SAS) AF: 0.778 AC: 49125 AN: 63118

European-Finnish (FIN) AF: 0.837 AC: 32489 AN: 38812

Middle Eastern (MID) AF: 0.759 AC: 2995 AN: 3944

European-Non Finnish (NFE) AF: 0.818 AC: 337796 AN: 412978

Other (OTH) AF: 0.772 AC: 26053 AN: 33738

GnomAD4 genome AF: 0.716 AC: 108966 AN: 152202 Hom.: 40294 Cov.: 33 AF XY: 0.713 AC XY: 53054 AN XY: 74408

African (AFR) AF: 0.562 AC: 23321 AN: 41488

American (AMR) AF: 0.648 AC: 9916 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2895 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2208 AN: 5186

South Asian (SAS) AF: 0.759 AC: 3657 AN: 4820

European-Finnish (FIN) AF: 0.847 AC: 8991 AN: 10616

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55571 AN: 68018

Other (OTH) AF: 0.724 AC: 1524 AN: 2106

Alfa AF: 0.771 Hom.: 97067

Bravo AF: 0.688

Asia WGS AF: 0.599 AC: 2079 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.7
DANN	Benign	0.86
PhyloP100		2.3
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: rs851797; hg19: chr1-242053042;