1-241889740-A-G

Position:

• chr1-241889740-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXO1	NM_130398.4	c.*140A>G		3_prime_UTR_variant	16/16	ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.*140A>G		3_prime_UTR_variant	16/16	1	NM_130398.4	ENSP00000355506	P2
EXO1	ENST00000348581.9	c.*140A>G		3_prime_UTR_variant	14/14	1		ENSP00000311873	P2
EXO1	ENST00000518483.5	c.*267A>G		3_prime_UTR_variant	14/14	1		ENSP00000430251	A2
EXO1	ENST00000518741.1	n.152-2784A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.606

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.778

Gnomad4 FIN exome AF: 0.837

Gnomad4 NFE exome AF: 0.818

Gnomad4 OTH exome AF: 0.772

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

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.724

Alfa AF: 0.787 Hom.: 67451

Bravo AF: 0.688

Asia WGS AF: 0.599 AC: 2079 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.7
DANN	Benign	0.86

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: rs851797; hg19: chr1-242053042;