11-36594508-G-C

Variant names:

• chr11-36594508-G-C
• rs116109232
• NM_138787.4:c.-108G>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138787.4(IFTAP):​c.-108G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00914 in 329,184 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (63 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (7 hom.)
• Consequence: IFTAP NM_138787.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 11-36594508-G-C is Benign according to our data. Variant chr11-36594508-G-C is described in ClinVar as [Benign]. Clinvar id is 1277632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFTAP	NM_138787.4	c.-108G>C		5_prime_UTR_variant	Exon 1 of 6	ENST00000334307.10	NP_620142.2
RAG2	NM_000536.4	c.-27-313C>G		intron_variant	Intron 1 of 1	ENST00000311485.8	NP_000527.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFTAP	ENST00000334307	c.-108G>C		5_prime_UTR_variant	Exon 1 of 6	1	NM_138787.4	ENSP00000334848.5
RAG2	ENST00000311485.8	c.-27-313C>G		intron_variant	Intron 1 of 1	1	NM_000536.4	ENSP00000308620.4

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2524 AN: 152158 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00861

GnomAD4 exome AF: 0.00272 AC: 481 AN: 176908 Hom.: 7 Cov.: 0 AF XY: 0.00217 AC XY: 204 AN XY: 93918

Gnomad4 AFR exome AF: 0.0632

Gnomad4 AMR exome AF: 0.00484

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000896

Gnomad4 FIN exome AF: 0.000378

Gnomad4 NFE exome AF: 0.000286

Gnomad4 OTH exome AF: 0.00267

GnomAD4 genome AF: 0.0166 AC: 2528 AN: 152276 Hom.: 63 Cov.: 32 AF XY: 0.0159 AC XY: 1182 AN XY: 74468

Gnomad4 AFR AF: 0.0574

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.0126 Hom.: 3

Bravo AF: 0.0184

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.51

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: rs116109232; hg19: chr11-36616058;