7-30455006-T-C

Variant names:

• chr7-30455006-T-C
• rs2075819
• NM_006092.4:c.376+131A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006092.4(NOD1):​c.376+131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 851,424 control chromosomes in the GnomAD database, including 40,280 homozygotes. 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 0.33 (9241 hom., cov: 32)
  • Exomes 𝑓: 0.29 (31039 hom.)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 12 publications found

Genes affected

NOD1 (HGNC:16390): (nucleotide binding oligomerization domain containing 1) This gene encodes a member of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family of proteins. The encoded protein plays a role in innate immunity by acting as a pattern-recognition receptor (PRR) that binds bacterial peptidoglycans and initiates inflammation. This protein has also been implicated in the immune response to viral and parasitic infection. Major structural features of this protein include an N-terminal caspase recruitment domain (CARD), a centrally located nucleotide-binding domain (NBD), and 10 tandem leucine-rich repeats (LRRs) in its C terminus. The CARD is involved in apoptotic signaling, LRRs participate in protein-protein interactions, and mutations in the NBD may affect the process of oligomerization and subsequent function of the LRR domain. Mutations in this gene are associated with asthma, inflammatory bowel disease, Behcet disease and sarcoidosis in human patients. [provided by RefSeq, Aug 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD1	NM_006092.4	c.376+131A>G		intron_variant	Intron 5 of 13	ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.376+131A>G		intron_variant	Intron 5 of 13	1	NM_006092.4	ENSP00000222823.4
NOD1	ENST00000434755.5	n.376+131A>G		intron_variant	Intron 5 of 14	2		ENSP00000416946.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50496 AN: 151902 Hom.: 9233 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.288 AC: 201666 AN: 699404 Hom.: 31039 AF XY: 0.293 AC XY: 105763 AN XY: 361164

African (AFR) AF: 0.485 AC: 8546 AN: 17632

American (AMR) AF: 0.187 AC: 4953 AN: 26434

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 4286 AN: 15690

East Asian (EAS) AF: 0.419 AC: 14559 AN: 34758

South Asian (SAS) AF: 0.398 AC: 22235 AN: 55876

European-Finnish (FIN) AF: 0.288 AC: 9742 AN: 33882

Middle Eastern (MID) AF: 0.398 AC: 968 AN: 2432

European-Non Finnish (NFE) AF: 0.264 AC: 126237 AN: 478700

Other (OTH) AF: 0.298 AC: 10140 AN: 34000

GnomAD4 genome AF: 0.332 AC: 50534 AN: 152020 Hom.: 9241 Cov.: 32 AF XY: 0.334 AC XY: 24815 AN XY: 74294

African (AFR) AF: 0.482 AC: 19987 AN: 41428

American (AMR) AF: 0.225 AC: 3444 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1896 AN: 5164

South Asian (SAS) AF: 0.409 AC: 1970 AN: 4820

European-Finnish (FIN) AF: 0.282 AC: 2986 AN: 10578

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18296 AN: 67972

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.296 Hom.: 19123

Bravo AF: 0.334

Asia WGS AF: 0.383 AC: 1329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs2075819; hg19: chr7-30494622; COSMIC: COSV56112252; COSMIC: COSV56112252;