rs4905087

chr14-93779303-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_178013.4(PRIMA1):c.102T>C(p.His34=) 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:3
• Conservation: PhyloP100: -1.16

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIMA1	NM_178013.4	c.102T>C	p.His34=	synonymous_variant	3/5	ENST00000393140.6
PRIMA1	XM_011536456.3	c.102T>C	p.His34=	synonymous_variant	3/5
PRIMA1	XM_047430966.1	c.102T>C	p.His34=	synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMA1	ENST00000393140.6	c.102T>C	p.His34=	synonymous_variant	3/5	1	NM_178013.4	P1
PRIMA1	ENST00000393143.5	c.102T>C	p.His34=	synonymous_variant	2/4	1		P1
PRIMA1	ENST00000316227.3	c.102T>C	p.His34=	synonymous_variant	2/5	1
PRIMA1	ENST00000477603.5	c.102T>C	p.His34=	synonymous_variant, NMD_transcript_variant	3/6	1

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

GnomAD3 exomes AF: 0.686 AC: 130850 AN: 190836 Hom.: 46652 AF XY: 0.692 AC XY: 73150 AN XY: 105656

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 SAS exome AF: 0.605

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

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.768

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.788

Gnomad4 NFE exome AF: 0.778

Gnomad4 OTH exome AF: 0.730

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

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.697

Alfa AF: 0.739 Hom.: 12358

Bravo AF: 0.696

Asia WGS AF: 0.499 AC: 1732 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -

Sleep-related hypermotor epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.94
Dann	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs4905087; hg19: chr14-94245649; COSMIC: COSV60263371;