NM_001080444.2:c.1128+168G>A

Variant names:

• chr21-39793781-G-A
• rs7278863
• NM_001080444.2:c.1128+168G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080444.2(IGSF5):​c.1128+168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,216 control chromosomes in the GnomAD database, including 813 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 0.10 (813 hom., cov: 32)
• Consequence: IGSF5 NM_001080444.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 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.1128+168G>A		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.1128+168G>A		intron	N/A	ENSP00000369962.4
	IGSF5	ENST00000459922.1	TSL:2	n.550+168G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15895 AN: 152098 Hom.: 809 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0454

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.105 AC: 15920 AN: 152216 Hom.: 813 Cov.: 32 AF XY: 0.103 AC XY: 7684 AN XY: 74426

African (AFR) AF: 0.122 AC: 5078 AN: 41516

American (AMR) AF: 0.0904 AC: 1382 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3472

East Asian (EAS) AF: 0.0455 AC: 236 AN: 5186

South Asian (SAS) AF: 0.0827 AC: 399 AN: 4824

European-Finnish (FIN) AF: 0.105 AC: 1116 AN: 10598

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7054 AN: 68004

Other (OTH) AF: 0.117 AC: 247 AN: 2114

Alfa AF: 0.0977 Hom.: 913

Bravo AF: 0.104

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.026
DANN	Benign	0.36
PhyloP100		-1.3
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: rs7278863; hg19: chr21-41165708;