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):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 37

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014334.4. 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
	FRRS1L	NM_014334.4	MANE Select	c.-3_-2delCGinsGC		5_prime_UTR	Exon 1 of 5	NP_055149.3	Q9P0K9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRRS1L	ENST00000561981.5	TSL:1 MANE Select	c.-3_-2delCGinsGC		5_prime_UTR	Exon 1 of 5	ENSP00000477141.2	Q9P0K9
	FRRS1L	ENST00000642299.1		n.-210_-209delCGinsGC		upstream_gene	N/A	ENSP00000495137.1	A0A2R8Y5Y6
	FRRS1L	ENST00000644747.1		n.-138_-137delCGinsGC		upstream_gene	N/A	ENSP00000493964.1	A0A2R8Y4E4

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Developmental and epileptic encephalopathy, 37 (2)
-	-	1	FRRS1L-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;