rs1208517

Variant names:

• chr1-185303351-C-T
• rs1208517
• NM_006469.5:c.766-1788G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367498.8(IVNS1ABP):​c.766-1788G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,084 control chromosomes in the GnomAD database, including 1,111 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 0.10 (1111 hom., cov: 32)
• Consequence: IVNS1ABP ENST00000367498.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 5 publications found

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]

IVNS1ABP Gene-Disease associations (from GenCC):

• immunodeficiency 70

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367498.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IVNS1ABP	NM_006469.5	MANE Select	c.766-1788G>A		intron	N/A	NP_006460.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IVNS1ABP	ENST00000367498.8	TSL:1 MANE Select	c.766-1788G>A		intron	N/A	ENSP00000356468.3
	IVNS1ABP	ENST00000480769.5	TSL:1	n.966-1788G>A		intron	N/A
	IVNS1ABP	ENST00000718429.1		c.766-1788G>A		intron	N/A	ENSP00000520813.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15793 AN: 151966 Hom.: 1112 Cov.: 32

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.104 AC: 15783 AN: 152084 Hom.: 1111 Cov.: 32 AF XY: 0.102 AC XY: 7556 AN XY: 74348

African (AFR) AF: 0.0288 AC: 1194 AN: 41500

American (AMR) AF: 0.113 AC: 1724 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0435 AC: 210 AN: 4826

European-Finnish (FIN) AF: 0.113 AC: 1201 AN: 10592

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10419 AN: 67944

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.135 Hom.: 1986

Bravo AF: 0.0983

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1208517; hg19: chr1-185272483; COSMIC: COSV62249900; COSMIC: COSV62249900;