rs992319972

Variant names:

• chr2-32224460-G-A
• rs992319972
• NM_001199138.2:c.*13C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-32224460-G-A
• chr2-32224460-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001199138.2(NLRC4):​c.*13C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000959 in 1,564,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: NLRC4 NM_001199138.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 0 publications found

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]

SLC30A6 (HGNC:19305): (solute carrier family 30 member 6) This gene encodes a member of a family of proteins that function as zinc transporters. This protein can regulate subcellular levels of zinc in the Golgi and vesicles. Expression of this gene is altered in the Alzheimer's disease brain plaques. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0000092 (13/1412408) while in subpopulation AFR AF = 0.000157 (5/31804). AF 95% confidence interval is 0.000061. There are 0 homozygotes in GnomAdExome4. There are 9 alleles in the male GnomAdExome4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199138.2. 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
	NLRC4	NM_001199138.2	MANE Select	c.*13C>T		3_prime_UTR	Exon 9 of 9	NP_001186067.1	Q9NPP4-1
	NLRC4	NM_001199139.1		c.*13C>T		3_prime_UTR	Exon 9 of 9	NP_001186068.1	Q9NPP4-1
	NLRC4	NM_021209.4		c.*13C>T		3_prime_UTR	Exon 9 of 9	NP_067032.3	Q9NPP4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRC4	ENST00000402280.6	TSL:1 MANE Select	c.*13C>T		3_prime_UTR	Exon 9 of 9	ENSP00000385428.1	Q9NPP4-1
	NLRC4	ENST00000360906.9	TSL:1	c.*13C>T		3_prime_UTR	Exon 9 of 9	ENSP00000354159.5	Q9NPP4-1
	NLRC4	ENST00000342905.10	TSL:1	c.*13C>T		3_prime_UTR	Exon 8 of 8	ENSP00000339666.6	Q9NPP4-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151942 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000136 AC: 3 AN: 220508 AF XY: 0.0000168

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000193

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000920 AC: 13 AN: 1412408 Hom.: 0 Cov.: 27 AF XY: 0.0000129 AC XY: 9 AN XY: 699724

African (AFR) AF: 0.000157 AC: 5 AN: 31804

American (AMR) AF: 0.00 AC: 0 AN: 37348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23790

East Asian (EAS) AF: 0.0000516 AC: 2 AN: 38770

South Asian (SAS) AF: 0.00 AC: 0 AN: 78454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 0.00000460 AC: 5 AN: 1086662

Other (OTH) AF: 0.0000172 AC: 1 AN: 58120

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151942 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74188

African (AFR) AF: 0.0000483 AC: 2 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.43
PhyloP100		-0.43

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

Other links and lift over

dbSNP: rs992319972; hg19: chr2-32449529; COSMIC: COSV99249596; COSMIC: COSV99249596;