chr21-39754760-T-C

Position:

• chr21-39754760-T-C

Variant summary

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

The NM_001080444.2(IGSF5):​c.100+8462T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,248 control chromosomes in the GnomAD database, including 1,090 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 0.12 (1090 hom., cov: 33)
• Consequence: IGSF5 NM_001080444.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF5	NM_001080444.2	c.100+8462T>C		intron_variant		ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1	c.371-10775T>C		intron_variant			XP_047296655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF5	ENST00000380588.5	c.100+8462T>C		intron_variant		1	NM_001080444.2	ENSP00000369962.4
IGSF5	ENST00000479378.1	n.206+3383T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17925 AN: 152130 Hom.: 1087 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.118 AC: 17942 AN: 152248 Hom.: 1090 Cov.: 33 AF XY: 0.116 AC XY: 8671 AN XY: 74446

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.136

Alfa AF: 0.119 Hom.: 1567

Bravo AF: 0.116

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.013
DANN	Benign	0.28

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: rs2837156; hg19: chr21-41126687;