rs4905087

Variant names:

• chr14-93779303-A-G
• rs4905087
• NM_178013.4:c.102T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_178013.4(PRIMA1):​c.102T>C​(p.His34His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,546,064 control chromosomes in the GnomAD database, including 437,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38596 hom., cov: 27)
  • Exomes 𝑓: 0.75 (398557 hom.)
• Consequence: PRIMA1 NM_178013.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.16
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 14-93779303-A-G is Benign according to our data. Variant chr14-93779303-A-G is described in ClinVar as Benign. ClinVar VariationId is 586376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 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.102T>C	p.His34His	synonymous	Exon 3 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.102T>C	p.His34His	synonymous	Exon 3 of 5	ENSP00000376848.1	Q86XR5-1
	PRIMA1	ENST00000393143.5	TSL:1	c.102T>C	p.His34His	synonymous	Exon 2 of 4	ENSP00000376851.1	Q86XR5-1
	PRIMA1	ENST00000316227.3	TSL:1	c.102T>C	p.His34His	synonymous	Exon 2 of 5	ENSP00000320948.3	Q86XR5-2

Frequencies

GnomAD3 genomes AF: 0.708 AC: 106910 AN: 151040 Hom.: 38563 Cov.: 27

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.703

GnomAD2 exomes AF: 0.686 AC: 130850 AN: 190836 AF XY: 0.692

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.763

Gnomad EAS exome AF: 0.266

Gnomad FIN exome AF: 0.789

Gnomad NFE exome AF: 0.762

Gnomad OTH exome AF: 0.714

GnomAD4 exome AF: 0.750 AC: 1046514 AN: 1394906 Hom.: 398557 Cov.: 36 AF XY: 0.748 AC XY: 517787 AN XY: 692360

African (AFR) AF: 0.623 AC: 18000 AN: 28914

American (AMR) AF: 0.613 AC: 20499 AN: 33458

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 18711 AN: 24358

East Asian (EAS) AF: 0.340 AC: 11835 AN: 34836

South Asian (SAS) AF: 0.627 AC: 47381 AN: 75578

European-Finnish (FIN) AF: 0.788 AC: 39995 AN: 50766

Middle Eastern (MID) AF: 0.791 AC: 4434 AN: 5604

European-Non Finnish (NFE) AF: 0.778 AC: 843533 AN: 1083692

Other (OTH) AF: 0.730 AC: 42126 AN: 57700

GnomAD4 genome AF: 0.708 AC: 106987 AN: 151158 Hom.: 38596 Cov.: 27 AF XY: 0.706 AC XY: 52113 AN XY: 73818

African (AFR) AF: 0.638 AC: 26209 AN: 41060

American (AMR) AF: 0.687 AC: 10433 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2643 AN: 3460

East Asian (EAS) AF: 0.322 AC: 1648 AN: 5112

South Asian (SAS) AF: 0.603 AC: 2869 AN: 4758

European-Finnish (FIN) AF: 0.797 AC: 8340 AN: 10462

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52414 AN: 67826

Other (OTH) AF: 0.697 AC: 1461 AN: 2096

Alfa AF: 0.736 Hom.: 74602

Bravo AF: 0.696

Asia WGS AF: 0.499 AC: 1732 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Familial sleep-related hypermotor epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.94
DANN	Benign	0.30
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
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: rs4905087; hg19: chr14-94245649; COSMIC: COSV60263371;