rs1887197

Variant names:

• chr14-93721486-C-T
• rs1887197
• NM_178013.4:c.420G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-93721486-C-T
• chr14-93721486-C-A
• chr14-93721486-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_178013.4(PRIMA1):​c.420G>A​(p.Ser140Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,612,388 control chromosomes in the GnomAD database, including 323,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26673 hom., cov: 31)
  • Exomes 𝑓: 0.63 (296338 hom.)
• Consequence: PRIMA1 NM_178013.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.83
• Publications: 19 publications found

Genes affected

PRIMA1 (HGNC:18319): (proline rich membrane anchor 1) The product of this gene functions to organize acetylcholinesterase (AChE) into tetramers, and to anchor AChE at neural cell membranes. [provided by RefSeq, Nov 2008]

PRIMA1 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 14-93721486-C-T is Benign according to our data. Variant chr14-93721486-C-T is described in ClinVar as Benign. ClinVar VariationId is 586377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMA1	NM_178013.4	MANE Select	c.420G>A	p.Ser140Ser	synonymous	Exon 5 of 5	NP_821092.1	Q86XR5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMA1	ENST00000393140.6	TSL:1 MANE Select	c.420G>A	p.Ser140Ser	synonymous	Exon 5 of 5	ENSP00000376848.1	Q86XR5-1
	PRIMA1	ENST00000393143.5	TSL:1	c.420G>A	p.Ser140Ser	synonymous	Exon 4 of 4	ENSP00000376851.1	Q86XR5-1
	PRIMA1	ENST00000316227.3	TSL:1	c.*216G>A		3_prime_UTR	Exon 5 of 5	ENSP00000320948.3	Q86XR5-2

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88386 AN: 151830 Hom.: 26667 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.610

GnomAD2 exomes AF: 0.607 AC: 152360 AN: 251012 AF XY: 0.610

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.728

Gnomad EAS exome AF: 0.328

Gnomad FIN exome AF: 0.632

Gnomad NFE exome AF: 0.658

Gnomad OTH exome AF: 0.630

GnomAD4 exome AF: 0.633 AC: 924802 AN: 1460440 Hom.: 296338 Cov.: 41 AF XY: 0.632 AC XY: 459312 AN XY: 726606

African (AFR) AF: 0.419 AC: 14006 AN: 33448

American (AMR) AF: 0.667 AC: 29810 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 18933 AN: 26122

East Asian (EAS) AF: 0.349 AC: 13839 AN: 39696

South Asian (SAS) AF: 0.550 AC: 47446 AN: 86208

European-Finnish (FIN) AF: 0.629 AC: 33533 AN: 53310

Middle Eastern (MID) AF: 0.669 AC: 3850 AN: 5758

European-Non Finnish (NFE) AF: 0.654 AC: 726090 AN: 1110868

Other (OTH) AF: 0.618 AC: 37295 AN: 60340

GnomAD4 genome AF: 0.582 AC: 88431 AN: 151948 Hom.: 26673 Cov.: 31 AF XY: 0.583 AC XY: 43262 AN XY: 74250

African (AFR) AF: 0.428 AC: 17757 AN: 41450

American (AMR) AF: 0.671 AC: 10256 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2514 AN: 3468

East Asian (EAS) AF: 0.342 AC: 1765 AN: 5156

South Asian (SAS) AF: 0.547 AC: 2616 AN: 4780

European-Finnish (FIN) AF: 0.636 AC: 6710 AN: 10558

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44779 AN: 67934

Other (OTH) AF: 0.603 AC: 1273 AN: 2112

Alfa AF: 0.632 Hom.: 88953

Bravo AF: 0.577

Asia WGS AF: 0.445 AC: 1555 AN: 3478

EpiCase AF: 0.666

EpiControl AF: 0.666

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Familial sleep-related hypermotor epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.13
DANN	Benign	0.61
PhyloP100		-1.8
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: rs1887197; hg19: chr14-94187832; COSMIC: COSV60262844;