rs1554736515

Variant names:

• chr9-109167140-CG-GC
• rs1554736515
• NM_014334.4:c.-3_-2delCGinsGC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014334.4(FRRS1L):​c.-3_-2delCGinsGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.997 in 32,141 alleles, including 16,070 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

• Frequency: GnomAD MNV: 𝑓 1.0 Genomes: not found (cov: 25)
• Consequence: FRRS1L NM_014334.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.560
• Publications: 1 publications found

Genes affected

FRRS1L (HGNC:1362): (ferric chelate reductase 1 like) This gene encodes a component of the outer-core of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor protein in the brain. The encoded protein is thought to interact with inner-core components of the receptor, and play a role in the modulation of glutamate signaling. Mutations in this gene are associated with early infantile epileptic encephalopathy 37. [provided by RefSeq, Jul 2016]

FRRS1L Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 37

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 9-109167140-CG-GC is Benign according to our data. Variant chr9-109167140-CG-GC is described in ClinVar as Benign. ClinVar VariationId is 476298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdMnv highest population allele frequency = 0.997 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRRS1L	NM_014334.4	c.-3_-2delCGinsGC		5_prime_UTR_variant	Exon 1 of 5	ENST00000561981.5	NP_055149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRRS1L	ENST00000561981.5	c.-3_-2delCGinsGC		5_prime_UTR_variant	Exon 1 of 5	1	NM_014334.4	ENSP00000477141.2
FRRS1L	ENST00000642299.1	n.-210_-209delCGinsGC		upstream_gene_variant				ENSP00000495137.1
FRRS1L	ENST00000644747.1	n.-138_-137delCGinsGC		upstream_gene_variant				ENSP00000493964.1

Frequencies

GnomAD3 genomes Cov.: 25

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

GnomAD4 genome Cov.: 25

GnomAD MNV AF: 0.997 AC: 32141 Hom.: 16070

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 37 Benign:2

-

Pathology and Clinical Laboratory Medicine, King Fahad Medical City

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FRRS1L-related disorder Benign:1

Oct 01, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Sep 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1554736515; hg19: chr9-111929420; COSMIC: COSV105308536; COSMIC: COSV105308536;