chr21-39800239-C-T

Position:

• chr21-39800239-C-T

Variant summary

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

The NM_001080444.2(IGSF5):​c.1129-1023C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,148 control chromosomes in the GnomAD database, including 6,774 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 0.27 (6774 hom., cov: 33)
• Consequence: IGSF5 NM_001080444.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF5	NM_001080444.2	c.1129-1023C>T		intron_variant		ENST00000380588.5
IGSF5	XM_047440699.1	c.1399-1023C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF5	ENST00000380588.5	c.1129-1023C>T		intron_variant		1	NM_001080444.2	P1
IGSF5	ENST00000459922.1	n.551-1023C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40386 AN: 152030 Hom.: 6756 Cov.: 33

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.266 AC: 40421 AN: 152148 Hom.: 6774 Cov.: 33 AF XY: 0.273 AC XY: 20309 AN XY: 74388

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.274

Alfa AF: 0.283 Hom.: 3366

Bravo AF: 0.269

Asia WGS AF: 0.392 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Benign	0.65

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: rs2837227; hg19: chr21-41172166;