rs10989019

Positions:

• chr9-100214259-T-C

Variant summary

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

The NM_014425.5(INVS):​c.274-11803T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,126 control chromosomes in the GnomAD database, including 4,580 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 0.19 (4580 hom., cov: 31)
• Consequence: INVS NM_014425.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INVS	NM_014425.5	c.274-11803T>C		intron_variant		ENST00000262457.7
INVS	NM_001318381.2	c.-103-1142T>C		intron_variant
INVS	NM_001318382.2	c.-716-11803T>C		intron_variant
INVS	NR_134606.2	n.472-11803T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INVS	ENST00000262457.7	c.274-11803T>C		intron_variant		1	NM_014425.5	A2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29492 AN: 152008 Hom.: 4566 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.194 AC: 29549 AN: 152126 Hom.: 4580 Cov.: 31 AF XY: 0.190 AC XY: 14122 AN XY: 74410

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0478

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.157

Alfa AF: 0.124 Hom.: 886

Bravo AF: 0.201

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.48

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: rs10989019; hg19: chr9-102976541;