rs1233284

Variant names:

• chr2-189825045-G-A
• rs1233284
• NM_000534.5:c.582+6865G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-189825045-G-A
• chr2-189825045-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000534.5(PMS1):​c.582+6865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,834 control chromosomes in the GnomAD database, including 11,222 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 0.36 (11222 hom., cov: 32)
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 18 publications found

Genes affected

PMS1 (HGNC:9121): (PMS1 homolog 1, mismatch repair system component) This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein. Mutations in this gene cause hereditary nonpolyposis colorectal cancer type 3 (HNPCC3) either alone or in combination with mutations in other genes involved in the HNPCC phenotype, which is also known as Lynch syndrome. [provided by RefSeq, Jul 2008]

PMS1 Gene-Disease associations (from GenCC):

• Lynch syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMS1	NM_000534.5	c.582+6865G>A		intron_variant	Intron 5 of 12	ENST00000441310.7	NP_000525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMS1	ENST00000441310.7	c.582+6865G>A		intron_variant	Intron 5 of 12	1	NM_000534.5	ENSP00000406490.3

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54321 AN: 151716 Hom.: 11199 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.358 AC: 54374 AN: 151834 Hom.: 11222 Cov.: 32 AF XY: 0.357 AC XY: 26447 AN XY: 74174

African (AFR) AF: 0.579 AC: 23988 AN: 41434

American (AMR) AF: 0.316 AC: 4825 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 912 AN: 3460

East Asian (EAS) AF: 0.283 AC: 1462 AN: 5172

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4824

European-Finnish (FIN) AF: 0.302 AC: 3166 AN: 10486

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17920 AN: 67884

Other (OTH) AF: 0.343 AC: 724 AN: 2108

Alfa AF: 0.340 Hom.: 4955

Bravo AF: 0.367

Asia WGS AF: 0.295 AC: 1025 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.79
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs1233284; hg19: chr2-190689771;