11-36598299-CT-C

Variant names:

• chr11-36598299-CT-C
• rs199509458
• NM_138787.4:c.-24+3716delT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_138787.4(IFTAP):​c.-24+3716delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 151,318 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFTAP NM_138787.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.788

Genes affected

IFTAP (HGNC:25142): (intraflagellar transport associated protein) This gene encodes a protein that was identified as a cellular interacting partner of non-structural protein 10 of the severe acute respiratory syndrome coronavirus (SARS-CoV). The encoded protein may function as a negative regulator of transcription. There is a pseudogene for this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

RAG2 (HGNC:9832): (recombination activating 2) This gene encodes a protein that is involved in the initiation of V(D)J recombination during B and T cell development. This protein forms a complex with the product of the adjacent recombination activating gene 1, and this complex can form double-strand breaks by cleaving DNA at conserved recombination signal sequences. The recombination activating gene 1 component is thought to contain most of the catalytic activity, while the N-terminal of the recombination activating gene 2 component is thought to form a six-bladed propeller in the active core that serves as a binding scaffold for the tight association of the complex with DNA. A C-terminal plant homeodomain finger-like motif in this protein is necessary for interactions with chromatin components, specifically with histone H3 that is trimethylated at lysine 4. Mutations in this gene cause Omenn syndrome, a form of severe combined immunodeficiency associated with autoimmune-like symptoms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-36598299-CT-C is Benign according to our data. Variant chr11-36598299-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1217941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0121 (1836/151318) while in subpopulation EAS AF= 0.0314 (161/5124). AF 95% confidence interval is 0.0275. There are 20 homozygotes in gnomad4. There are 831 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFTAP	NM_138787.4	c.-24+3716delT		intron_variant	Intron 1 of 5	ENST00000334307.10	NP_620142.2
RAG2	NM_000536.4	c.-226delA		upstream_gene_variant		ENST00000311485.8	NP_000527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFTAP	ENST00000334307.10	c.-24+3708delT		intron_variant	Intron 1 of 5	1	NM_138787.4	ENSP00000334848.5
RAG2	ENST00000311485.8	c.-226delA		upstream_gene_variant		1	NM_000536.4	ENSP00000308620.4

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1834 AN: 151200 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00401

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.0315

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.00201

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0111

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0121 AC: 1836 AN: 151318 Hom.: 20 Cov.: 32 AF XY: 0.0112 AC XY: 831 AN XY: 73900

Gnomad4 AFR AF: 0.00405

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.0314

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.00201

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.000994 Hom.: 0

Bravo AF: 0.0127

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 12, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs199509458; hg19: chr11-36619849;