rs141245080

Variant names:

• chr1-200891603-G-A
• rs141245080
• ENST00000367342.8:c.105G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-200891603-G-A
• chr1-200891603-G-C
• chr1-200891603-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000367342.8(INAVA):​c.105G>A​(p.Arg35Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,562,954 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R35R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0093 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (25 hom.)
• Consequence: INAVA ENST00000367342.8 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.588
• Publications: 2 publications found

Genes affected

INAVA (HGNC:25599): (innate immunity activator) Involved in several processes, including nucleotide-binding activity oligomerization domain containing 2 signaling pathway; positive regulation of cytokine production; and positive regulation of intracellular signal transduction. Located in cytoplasm and nucleus. Implicated in inflammatory bowel disease 29. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-200891603-G-A is Benign according to our data. Variant chr1-200891603-G-A is described in ClinVar as [Benign]. Clinvar id is 709585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.588 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00933 (1421/152338) while in subpopulation AFR AF = 0.0318 (1321/41572). AF 95% confidence interval is 0.0304. There are 18 homozygotes in GnomAd4. There are 692 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INAVA	NM_018265.4	c.63G>A	p.Arg21Arg	synonymous_variant	Exon 1 of 10		NP_060735.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INAVA	ENST00000367342.8	c.105G>A	p.Arg35Arg	synonymous_variant	Exon 1 of 10	1		ENSP00000356311.5
INAVA	ENST00000451872.6	c.-10+201G>A		intron_variant	Intron 1 of 4	3		ENSP00000397255.2
INAVA	ENST00000532631.5	c.-95+201G>A		intron_variant	Intron 1 of 2	3		ENSP00000431682.1

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1415 AN: 152220 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

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: 0.000220

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00270 AC: 510 AN: 189228 AF XY: 0.00206

Gnomad AFR exome AF: 0.0361

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000233

Gnomad OTH exome AF: 0.000237

GnomAD4 exome AF: 0.00102 AC: 1436 AN: 1410616 Hom.: 25 Cov.: 31 AF XY: 0.000888 AC XY: 621 AN XY: 699300

African (AFR) AF: 0.0351 AC: 1060 AN: 30166

American (AMR) AF: 0.00184 AC: 71 AN: 38630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22718

East Asian (EAS) AF: 0.00 AC: 0 AN: 36116

South Asian (SAS) AF: 0.000127 AC: 10 AN: 78938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51550

Middle Eastern (MID) AF: 0.00127 AC: 7 AN: 5500

European-Non Finnish (NFE) AF: 0.000152 AC: 165 AN: 1088834

Other (OTH) AF: 0.00211 AC: 123 AN: 58164

GnomAD4 genome AF: 0.00933 AC: 1421 AN: 152338 Hom.: 18 Cov.: 33 AF XY: 0.00929 AC XY: 692 AN XY: 74496

African (AFR) AF: 0.0318 AC: 1321 AN: 41572

American (AMR) AF: 0.00451 AC: 69 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68032

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.000644 Hom.: 0

Bravo AF: 0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 17, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		0.59
PromoterAI		-0.22	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141245080; hg19: chr1-200860731;