rs7039994

Positions:

• chr9-100288923-C-T

Variant summary

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

The NM_014425.5(INVS):​c.2069-3403C>T 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 152,002 control chromosomes in the GnomAD database, including 3,559 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 (3559 hom., cov: 32)
• Consequence: INVS NM_014425.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43

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=-1.09).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INVS	NM_014425.5	c.2069-3403C>T		intron_variant		ENST00000262457.7
INVS	NM_001318381.2	c.1781-3403C>T		intron_variant
INVS	NM_001318382.2	c.1091-3403C>T		intron_variant
INVS	NR_134606.2	n.2267-3452C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INVS	ENST00000262457.7	c.2069-3403C>T		intron_variant		1	NM_014425.5	A2
INVS	ENST00000262456.6	c.2069-3403C>T		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29373 AN: 151884 Hom.: 3548 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.194 AC: 29425 AN: 152002 Hom.: 3559 Cov.: 32 AF XY: 0.188 AC XY: 13950 AN XY: 74296

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.00868

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.165

Alfa AF: 0.161 Hom.: 1360

Bravo AF: 0.198

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.34
DANN	Benign	0.56

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: rs7039994; hg19: chr9-103051205;