rs4150018

Variant names:

• chr1-241889319-T-A
• rs4150018
• NM_130398.4:c.2406-146T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-241889319-T-A
• chr1-241889319-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_130398.4(EXO1):​c.2406-146T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 711,226 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: EXO1 NM_130398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 8 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High AC in GnomAd4 at 177 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXO1	NM_130398.4	c.2406-146T>A		intron_variant	Intron 15 of 15	ENST00000366548.8	NP_569082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXO1	ENST00000366548.8	c.2406-146T>A		intron_variant	Intron 15 of 15	1	NM_130398.4	ENSP00000355506.3

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 177 AN: 151964 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.000113 AC: 63 AN: 559144 Hom.: 0 AF XY: 0.0000809 AC XY: 24 AN XY: 296502

African (AFR) AF: 0.00249 AC: 37 AN: 14888

American (AMR) AF: 0.000140 AC: 4 AN: 28504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17134

East Asian (EAS) AF: 0.00 AC: 0 AN: 31516

South Asian (SAS) AF: 0.0000183 AC: 1 AN: 54604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2294

European-Non Finnish (NFE) AF: 0.0000116 AC: 4 AN: 345798

Other (OTH) AF: 0.000573 AC: 17 AN: 29672

GnomAD4 genome AF: 0.00116 AC: 177 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.00108 AC XY: 80 AN XY: 74334

African (AFR) AF: 0.00422 AC: 175 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67972

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00 Hom.: 6948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		0.22

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: rs4150018; hg19: chr1-242052621;