rs1233255

chr2-189841366-A-C

Variant summary

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

The NM_000534.5(PMS1):c.583-2598A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,022 control chromosomes in the GnomAD database, including 5,869 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 0.26 (5869 hom., cov: 32)
• Consequence: PMS1 NM_000534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMS1	NM_000534.5	c.583-2598A>C		intron_variant		ENST00000441310.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMS1	ENST00000441310.7	c.583-2598A>C		intron_variant		1	NM_000534.5	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39871 AN: 151904 Hom.: 5864 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.263 AC: 39911 AN: 152022 Hom.: 5869 Cov.: 32 AF XY: 0.260 AC XY: 19287 AN XY: 74308

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.266

Alfa AF: 0.234 Hom.: 1246

Bravo AF: 0.266

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.094
Dann	Benign	0.41

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: rs1233255; hg19: chr2-190706092;