rs1735151

Positions:

• chr21-39751374-T-C
• chr21-39751374-T-A

Variant summary

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

The NM_001080444.2(IGSF5):​c.100+5076T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,180 control chromosomes in the GnomAD database, including 40,948 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 0.71 (40931 hom., cov: 33)
  • Exomes 𝑓: 0.87 (17 hom.)
• Consequence: IGSF5 NM_001080444.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

Genes affected

IGSF5 (HGNC:5952): (immunoglobulin superfamily member 5) Predicted to enable PDZ domain binding activity. Predicted to be involved in cell-cell adhesion. Predicted to be located in apical plasma membrane. Predicted to be integral component of membrane. Predicted to be active in bicellular tight junction and cell surface. [provided by Alliance of Genome Resources, Apr 2022]

IGSF5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF5	NM_001080444.2	c.100+5076T>C		intron_variant		ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1	c.371-14161T>C		intron_variant			XP_047296655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF5	ENST00000380588.5	c.100+5076T>C		intron_variant		1	NM_001080444.2	ENSP00000369962.4
IGSF5	ENST00000479378.1	n.203T>C		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107753 AN: 152016 Hom.: 40905 Cov.: 33

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.715

GnomAD4 exome AF: 0.870 AC: 40 AN: 46 Hom.: 17 Cov.: 0 AF XY: 0.906 AC XY: 29 AN XY: 32

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.886

GnomAD4 genome AF: 0.709 AC: 107816 AN: 152134 Hom.: 40931 Cov.: 33 AF XY: 0.713 AC XY: 52999 AN XY: 74380

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.714

Alfa AF: 0.813 Hom.: 57084

Bravo AF: 0.693

Asia WGS AF: 0.730 AC: 2540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.42
DANN	Benign	0.46

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: rs1735151; hg19: chr21-41123301;