rs2837175

Variant names:

• chr21-39760018-T-C
• rs2837175
• NM_001080444.2:c.101-5517T>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.101-5517T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,894 control chromosomes in the GnomAD database, including 11,936 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 0.39 (11936 hom., cov: 31)
• Consequence: IGSF5 NM_001080444.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF5	NM_001080444.2	c.101-5517T>C		intron_variant	Intron 2 of 8	ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1	c.371-5517T>C		intron_variant	Intron 3 of 9		XP_047296655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF5	ENST00000380588.5	c.101-5517T>C		intron_variant	Intron 2 of 8	1	NM_001080444.2	ENSP00000369962.4
IGSF5	ENST00000479378.1	n.207-5517T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59352 AN: 151776 Hom.: 11912 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.391 AC: 59415 AN: 151894 Hom.: 11936 Cov.: 31 AF XY: 0.395 AC XY: 29325 AN XY: 74218

African (AFR) AF: 0.390 AC: 16146 AN: 41414

American (AMR) AF: 0.521 AC: 7949 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1438 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2215 AN: 5148

South Asian (SAS) AF: 0.479 AC: 2302 AN: 4806

European-Finnish (FIN) AF: 0.386 AC: 4072 AN: 10546

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24004 AN: 67928

Other (OTH) AF: 0.373 AC: 786 AN: 2110

Alfa AF: 0.366 Hom.: 5489

Bravo AF: 0.402

Asia WGS AF: 0.457 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.83
PhyloP100		-0.51
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: rs2837175; hg19: chr21-41131945;