2-32224632-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_001199138.2(NLRC4):c.2916T>C(p.Phe972=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NLRC4 NM_001199138.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.197

Genes affected

NLRC4 (HGNC:16412): (NLR family CARD domain containing 4) This gene encodes a member of the caspase recruitment domain-containing NLR family. Family members play essential roles in innate immune response to a wide range of pathogenic organisms, tissue damage and other cellular stresses. Mutations in this gene result in autoinflammation with infantile enterocolitis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-32224632-A-G is Benign according to our data. Variant chr2-32224632-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1694377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.197 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRC4	NM_001199138.2	c.2916T>C	p.Phe972=	synonymous_variant	9/9	ENST00000402280.6
NLRC4	NM_001199139.1	c.2916T>C	p.Phe972=	synonymous_variant	9/9
NLRC4	NM_021209.4	c.2916T>C	p.Phe972=	synonymous_variant	9/9
NLRC4	NM_001302504.1	c.921T>C	p.Phe307=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRC4	ENST00000402280.6	c.2916T>C	p.Phe972=	synonymous_variant	9/9	1	NM_001199138.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autoinflammatory syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 05, 2020

- -

Periodic fever-infantile enterocolitis-autoinflammatory syndrome;C4015276:Familial cold autoinflammatory syndrome 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.8
Dann	Benign	0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-32449701;