1-241865799-T-C

Variant names:

• chr1-241865799-T-C
• rs2526698
• NM_130398.4:c.1042-1031T>C

Variant summary

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

The NM_130398.4(EXO1):​c.1042-1031T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,976 control chromosomes in the GnomAD database, including 20,333 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 0.51 (20333 hom., cov: 32)
• Consequence: EXO1 NM_130398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 9 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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXO1	NM_130398.4	c.1042-1031T>C		intron_variant	Intron 10 of 15	ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.1042-1031T>C		intron_variant	Intron 10 of 15	1	NM_130398.4	ENSP00000355506.3
EXO1	ENST00000348581.9	c.1042-1031T>C		intron_variant	Intron 8 of 13	1		ENSP00000311873.5
EXO1	ENST00000518483.5	c.1042-1031T>C		intron_variant	Intron 8 of 13	1		ENSP00000430251.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77856 AN: 151858 Hom.: 20302 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.513 AC: 77945 AN: 151976 Hom.: 20333 Cov.: 32 AF XY: 0.514 AC XY: 38203 AN XY: 74272

African (AFR) AF: 0.589 AC: 24414 AN: 41462

American (AMR) AF: 0.478 AC: 7299 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3466

East Asian (EAS) AF: 0.710 AC: 3670 AN: 5166

South Asian (SAS) AF: 0.449 AC: 2156 AN: 4804

European-Finnish (FIN) AF: 0.497 AC: 5237 AN: 10532

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32168 AN: 67958

Other (OTH) AF: 0.509 AC: 1075 AN: 2110

Alfa AF: 0.477 Hom.: 9116

Bravo AF: 0.515

Asia WGS AF: 0.579 AC: 2009 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		2.0
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: rs2526698; hg19: chr1-242029101;