1-185308881-T-TA

Position:

• chr1-185308881-T-TA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006469.5(IVNS1ABP):​c.282-7_282-6insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,591,448 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: IVNS1ABP NM_006469.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.244

Genes affected

IVNS1ABP (HGNC:16951): (influenza virus NS1A binding protein) Involved in RNA splicing; negative regulation of protein ubiquitination; and response to virus. Located in cytosol. Implicated in immunodeficiency 70. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-185308881-T-TA is Benign according to our data. Variant chr1-185308881-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 3047896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 96 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IVNS1ABP	NM_006469.5	c.282-7_282-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000367498.8
IVNS1ABP	XM_047434070.1	c.282-7_282-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
IVNS1ABP	XM_047434096.1	c.15-7_15-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IVNS1ABP	ENST00000367498.8	c.282-7_282-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006469.5	P1
IVNS1ABP	ENST00000367497.1	c.282-7_282-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5
IVNS1ABP	ENST00000459929.5	n.849-7_849-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.000627 AC: 95 AN: 151592 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.000101 AC: 145 AN: 1439738 Hom.: 0 Cov.: 29 AF XY: 0.0000921 AC XY: 66 AN XY: 716420

Gnomad4 AFR exome AF: 0.00189

Gnomad4 AMR exome AF: 0.000265

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000361

Gnomad4 FIN exome AF: 0.0000585

Gnomad4 NFE exome AF: 0.0000554

Gnomad4 OTH exome AF: 0.000101

GnomAD4 genome AF: 0.000633 AC: 96 AN: 151710 Hom.: 0 Cov.: 32 AF XY: 0.000594 AC XY: 44 AN XY: 74128

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000475

Bravo AF: 0.000646

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

IVNS1ABP-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs748447429; hg19: chr1-185278013;