chr1-241848847-C-T

Position:

• chr1-241848847-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130398.4(EXO1):​c.-303C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,996 control chromosomes in the GnomAD database, including 16,618 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 0.46 (16617 hom., cov: 32)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: EXO1 NM_130398.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXO1	NM_130398.4	c.-303C>T		5_prime_UTR_variant	2/16	ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548	c.-303C>T		5_prime_UTR_variant	2/16	1	NM_130398.4	ENSP00000355506.3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70569 AN: 151868 Hom.: 16594 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.400 AC: 4 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.465 AC: 70637 AN: 151986 Hom.: 16617 Cov.: 32 AF XY: 0.466 AC XY: 34643 AN XY: 74268

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.475

Alfa AF: 0.455 Hom.: 15753

Bravo AF: 0.464

Asia WGS AF: 0.552 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1776177; hg19: chr1-242012149;