chr1-241865799-T-C

Position:

• chr1-241865799-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.71).
• 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/exons	MANE	Protein	UniProt
EXO1	NM_130398.4	c.1042-1031T>C		intron_variant		ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.1042-1031T>C		intron_variant		1	NM_130398.4	ENSP00000355506	P2
EXO1	ENST00000348581.9	c.1042-1031T>C		intron_variant		1		ENSP00000311873	P2
EXO1	ENST00000518483.5	c.1042-1031T>C		intron_variant		1		ENSP00000430251	A2

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

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.509

Alfa AF: 0.479 Hom.: 8293

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

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: rs2526698; hg19: chr1-242029101;