rs7278863

Positions:

• chr21-39793781-G-A
• chr21-39793781-G-T

Variant summary

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

The ENST00000380588.5(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 ENST00000380588.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF5	NM_001080444.2	c.1128+168G>A		intron_variant		ENST00000380588.5	NP_001073913.1
IGSF5	XM_047440699.1	c.1398+168G>A		intron_variant			XP_047296655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF5	ENST00000380588.5	c.1128+168G>A		intron_variant		1	NM_001080444.2	ENSP00000369962	P1
IGSF5	ENST00000459922.1	n.550+168G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0904

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.0827

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0953 Hom.: 647

Bravo AF: 0.104

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.026
DANN	Benign	0.36

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: rs7278863; hg19: chr21-41165708;