rs4149896

Positions:

• chr1-241857502-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXO1	NM_130398.4	c.543+20A>G		intron_variant		ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.543+20A>G		intron_variant		1	NM_130398.4	ENSP00000355506	P2

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

GnomAD3 exomes AF: 0.112 AC: 28041 AN: 251036 Hom.: 2646 AF XY: 0.105 AC XY: 14241 AN XY: 135744

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 SAS exome AF: 0.0944

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

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.0487

Gnomad4 EAS exome AF: 0.0970

Gnomad4 SAS exome AF: 0.0939

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0790

Gnomad4 OTH exome AF: 0.0772

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

Gnomad4 AFR AF: 0.0206

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.0537

Gnomad4 EAS AF: 0.0842

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.0835

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.089
DANN	Benign	0.40

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: rs4149896; hg19: chr1-242020804; COSMIC: COSV62216890; COSMIC: COSV62216890;