chr21-39754760-T-C

Variant names:

• chr21-39754760-T-C
• rs2837156
• NM_001080444.2:c.100+8462T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080444.2. 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
	IGSF5	NM_001080444.2	MANE Select	c.100+8462T>C		intron	N/A	NP_001073913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF5	ENST00000380588.5	TSL:1 MANE Select	c.100+8462T>C		intron	N/A	ENSP00000369962.4
	IGSF5	ENST00000479378.1	TSL:5	n.206+3383T>C		intron	N/A

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

African (AFR) AF: 0.134 AC: 5547 AN: 41540

American (AMR) AF: 0.100 AC: 1534 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3470

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5192

South Asian (SAS) AF: 0.127 AC: 611 AN: 4822

European-Finnish (FIN) AF: 0.113 AC: 1197 AN: 10604

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8144 AN: 68016

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.118 Hom.: 2335

Bravo AF: 0.116

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.013
DANN	Benign	0.28
PhyloP100		-3.2
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: rs2837156; hg19: chr21-41126687;