1-241857502-A-G

Variant names:

• chr1-241857502-A-G
• rs4149896
• NM_130398.4:c.543+20A>G

Variant summary

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

The NM_130398.4(EXO1):​c.543+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 1,604,528 control chromosomes in the GnomAD database, including 7,703 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 0.078 (719 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6984 hom.)
• Consequence: EXO1 NM_130398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.188 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.543+20A>G		intron	N/A	NP_569082.2
	EXO1	NM_006027.4		c.543+20A>G		intron	N/A	NP_006018.4
	EXO1	NM_001319224.2		c.543+20A>G		intron	N/A	NP_001306153.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXO1	ENST00000366548.8	TSL:1 MANE Select	c.543+20A>G		intron	N/A	ENSP00000355506.3
	EXO1	ENST00000348581.9	TSL:1	c.543+20A>G		intron	N/A	ENSP00000311873.5
	EXO1	ENST00000518483.5	TSL:1	c.543+20A>G		intron	N/A	ENSP00000430251.1

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11835 AN: 152018 Hom.: 714 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0537

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.0844

GnomAD2 exomes AF: 0.112 AC: 28041 AN: 251036 AF XY: 0.105

Gnomad AFR exome AF: 0.0183

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.0474

Gnomad EAS exome AF: 0.0752

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0824

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0860 AC: 124919 AN: 1452392 Hom.: 6984 Cov.: 27 AF XY: 0.0859 AC XY: 62078 AN XY: 723046

African (AFR) AF: 0.0150 AC: 500 AN: 33288

American (AMR) AF: 0.296 AC: 13190 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 1267 AN: 26030

East Asian (EAS) AF: 0.0970 AC: 3839 AN: 39570

South Asian (SAS) AF: 0.0939 AC: 8073 AN: 85972

European-Finnish (FIN) AF: 0.111 AC: 5902 AN: 53194

Middle Eastern (MID) AF: 0.0555 AC: 285 AN: 5134

European-Non Finnish (NFE) AF: 0.0790 AC: 87229 AN: 1104560

Other (OTH) AF: 0.0772 AC: 4634 AN: 60012

GnomAD4 genome AF: 0.0778 AC: 11840 AN: 152136 Hom.: 719 Cov.: 32 AF XY: 0.0810 AC XY: 6023 AN XY: 74370

African (AFR) AF: 0.0206 AC: 854 AN: 41520

American (AMR) AF: 0.194 AC: 2957 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0537 AC: 186 AN: 3466

East Asian (EAS) AF: 0.0842 AC: 436 AN: 5180

South Asian (SAS) AF: 0.0948 AC: 457 AN: 4820

European-Finnish (FIN) AF: 0.107 AC: 1129 AN: 10572

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0819 AC: 5571 AN: 68000

Other (OTH) AF: 0.0835 AC: 176 AN: 2108

Alfa AF: 0.0798 Hom.: 117

Bravo AF: 0.0833

Asia WGS AF: 0.0920 AC: 323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.089
DANN	Benign	0.40
PhyloP100		-0.66
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: rs4149896; hg19: chr1-242020804; COSMIC: COSV62216890; COSMIC: COSV62216890;