rs2806687

Variant names:

• chr9-100243533-T-C
• rs2806687
• NM_014425.5:c.906+854T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014425.5(INVS):​c.906+854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,846 control chromosomes in the GnomAD database, including 22,031 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 0.52 (22031 hom., cov: 31)
• Consequence: INVS NM_014425.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

Genes affected

INVS (HGNC:17870): (inversin) This gene encodes a protein containing multiple ankyrin domains and two IQ calmodulin-binding domains. The encoded protein may function in renal tubular development and function, and in left-right axis determination. This protein interacts with nephrocystin and infers a connection between primary cilia function and left-right axis determination. A similar protein in mice interacts with calmodulin. Mutations in this gene have been associated with nephronophthisis type 2. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INVS	NM_014425.5	c.906+854T>C		intron_variant	Intron 7 of 16	ENST00000262457.7	NP_055240.2
INVS	NM_001318381.2	c.618+854T>C		intron_variant	Intron 8 of 17		NP_001305310.1
INVS	NM_001318382.2	c.-84+854T>C		intron_variant	Intron 7 of 16		NP_001305311.1
INVS	NR_134606.2	n.1104+854T>C		intron_variant	Intron 7 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INVS	ENST00000262457.7	c.906+854T>C		intron_variant	Intron 7 of 16	1	NM_014425.5	ENSP00000262457.2
INVS	ENST00000262456.6	c.906+854T>C		intron_variant	Intron 7 of 17	5		ENSP00000262456.2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79442 AN: 151728 Hom.: 21987 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.524 AC: 79546 AN: 151846 Hom.: 22031 Cov.: 31 AF XY: 0.515 AC XY: 38192 AN XY: 74202

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.0963

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.507

Alfa AF: 0.515 Hom.: 3730

Bravo AF: 0.519

Asia WGS AF: 0.250 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs2806687; hg19: chr9-103005815;