rs7024375

Variant names:

• chr9-100099331-T-G
• rs7024375
• NM_014425.5:c.-110T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-100099331-T-G
• chr9-100099331-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014425.5(INVS):​c.-110T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 153,298 control chromosomes in the GnomAD database, including 3,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3478 hom., cov: 31)
  • Exomes 𝑓: 0.26 (43 hom.)
• Consequence: INVS NM_014425.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.634
• Publications: 18 publications found

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]

INVS Gene-Disease associations (from GenCC):

• nephronophthisis 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 9-100099331-T-G is Benign according to our data. Variant chr9-100099331-T-G is described in ClinVar as Benign. ClinVar VariationId is 364220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014425.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INVS	NM_014425.5	MANE Select	c.-110T>G		5_prime_UTR	Exon 1 of 17	NP_055240.2
	INVS	NM_001318381.2		c.-486T>G		5_prime_UTR	Exon 1 of 18	NP_001305310.1
	INVS	NM_001318382.2		c.-1099T>G		5_prime_UTR	Exon 1 of 17	NP_001305311.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INVS	ENST00000262457.7	TSL:1 MANE Select	c.-110T>G		5_prime_UTR	Exon 1 of 17	ENSP00000262457.2	Q9Y283-1
	INVS	ENST00000374921.3	TSL:1	c.-110T>G		5_prime_UTR	Exon 1 of 4	ENSP00000364056.3	Q9Y283-3
	INVS	ENST00000885859.1		c.-221T>G		5_prime_UTR	Exon 1 of 18	ENSP00000555918.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26656 AN: 151948 Hom.: 3477 Cov.: 31

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.262 AC: 323 AN: 1232 Hom.: 43 Cov.: 0 AF XY: 0.261 AC XY: 221 AN XY: 846

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.500 AC: 6 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 3 AN: 8

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 0.313 AC: 217 AN: 694

European-Finnish (FIN) AF: 0.500 AC: 5 AN: 10

Middle Eastern (MID) AF: 0.167 AC: 1 AN: 6

European-Non Finnish (NFE) AF: 0.170 AC: 77 AN: 452

Other (OTH) AF: 0.250 AC: 10 AN: 40

GnomAD4 genome AF: 0.175 AC: 26666 AN: 152066 Hom.: 3478 Cov.: 31 AF XY: 0.184 AC XY: 13655 AN XY: 74348

African (AFR) AF: 0.0528 AC: 2192 AN: 41522

American (AMR) AF: 0.269 AC: 4118 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3470

East Asian (EAS) AF: 0.643 AC: 3290 AN: 5118

South Asian (SAS) AF: 0.321 AC: 1547 AN: 4824

European-Finnish (FIN) AF: 0.215 AC: 2275 AN: 10596

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11897 AN: 67942

Other (OTH) AF: 0.182 AC: 384 AN: 2108

Alfa AF: 0.182 Hom.: 8044

Bravo AF: 0.178

Asia WGS AF: 0.436 AC: 1509 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Infantile nephronophthisis (1)
-	-	1	Kidney disorder (1)
-	-	1	Nephronophthisis (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.63
PromoterAI		-0.017	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7024375; hg19: chr9-102861613;