rs17036023

Positions:

• chr1-116587089-A-G

Variant summary

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

The NM_001007237.3(IGSF3):​c.2440+1605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 152,202 control chromosomes in the GnomAD database, including 408 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 0.041 (408 hom., cov: 32)
• Consequence: IGSF3 NM_001007237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

IGSF3 (HGNC:5950): (immunoglobulin superfamily member 3) The protein encoded by this gene is an immunoglobulin-like membrane protein containing several V-type Ig-like domains. A mutation in this gene has been associated with bilateral nasolacrimal duct obstruction (LCDD). [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF3	NM_001007237.3	c.2440+1605T>C		intron_variant		ENST00000369486.8	NP_001007238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF3	ENST00000369486.8	c.2440+1605T>C		intron_variant		1	NM_001007237.3	ENSP00000358498	P4
IGSF3	ENST00000318837.6	c.2500+1605T>C		intron_variant		2		ENSP00000321184	A1
IGSF3	ENST00000369483.5	c.2500+1605T>C		intron_variant		5		ENSP00000358495	A1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6191 AN: 152084 Hom.: 407 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0408 AC: 6203 AN: 152202 Hom.: 408 Cov.: 32 AF XY: 0.0391 AC XY: 2908 AN XY: 74436

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0496 Hom.: 67

Bravo AF: 0.0454

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17036023; hg19: chr1-117129711;