1-200891603-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The ENST00000367342.8(INAVA):​c.105G>C​(p.Arg35Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,562,952 control chromosomes in the GnomAD database, including 51 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 0.0043 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0070 (51 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-200891603-G-C is Benign according to our data. Variant chr1-200891603-G-C is described in ClinVar as [Benign]. Clinvar id is 779223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.588 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INAVA	NM_018265.4	c.63G>C	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>C	p.Arg35Arg	synonymous_variant	Exon 1 of 10	1		ENSP00000356311.5
INAVA	ENST00000451872.6	c.-10+201G>C		intron_variant	Intron 1 of 4	3		ENSP00000397255.2
INAVA	ENST00000532631.5	c.-95+201G>C		intron_variant	Intron 1 of 2	3		ENSP00000431682.1

Frequencies

GnomAD3 genomes AF: 0.00431 AC: 656 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00801

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00499 AC: 944 AN: 189228 AF XY: 0.00483

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.000479

Gnomad ASJ exome AF: 0.000176

Gnomad EAS exome AF: 0.0000758

Gnomad FIN exome AF: 0.00448

Gnomad NFE exome AF: 0.00926

Gnomad OTH exome AF: 0.00522

GnomAD4 exome AF: 0.00702 AC: 9896 AN: 1410608 Hom.: 51 Cov.: 31 AF XY: 0.00671 AC XY: 4693 AN XY: 699296

African (AFR) AF: 0.000862 AC: 26 AN: 30172

American (AMR) AF: 0.000544 AC: 21 AN: 38630

Ashkenazi Jewish (ASJ) AF: 0.000440 AC: 10 AN: 22718

East Asian (EAS) AF: 0.0000554 AC: 2 AN: 36114

South Asian (SAS) AF: 0.000355 AC: 28 AN: 78938

European-Finnish (FIN) AF: 0.00549 AC: 283 AN: 51550

Middle Eastern (MID) AF: 0.000364 AC: 2 AN: 5500

European-Non Finnish (NFE) AF: 0.00852 AC: 9277 AN: 1088822

Other (OTH) AF: 0.00425 AC: 247 AN: 58164

GnomAD4 genome AF: 0.00431 AC: 656 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.00392 AC XY: 292 AN XY: 74500

African (AFR) AF: 0.00135 AC: 56 AN: 41578

American (AMR) AF: 0.000392 AC: 6 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10632

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

European-Non Finnish (NFE) AF: 0.00801 AC: 545 AN: 68032

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00161 Hom.: 0

Bravo AF: 0.00402

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		0.59
PromoterAI		-0.087	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;