chr1-160091594-C-T

Position:

• chr1-160091594-C-T

Variant summary

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

The NM_052868.6(IGSF8):​c.*30G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 534,794 control chromosomes in the GnomAD database, including 4,130 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 0.099 (1001 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3129 hom.)
• Consequence: IGSF8 NM_052868.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

Genes affected

IGSF8 (HGNC:17813): (immunoglobulin superfamily member 8) This gene encodes a member the EWI subfamily of the immunoglobulin protein superfamily. Members of this family contain a single transmembrane domain, an EWI (Glu-Trp-Ile)-motif and a variable number of immunoglobulin domains. This protein interacts with the tetraspanins CD81 and CD9 and may regulate their role in certain cellular functions including cell migration and viral infection. The encoded protein may also function as a tumor suppressor by inhibiting the proliferation of certain cancers. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF8	NM_052868.6	c.*30G>A		3_prime_UTR_variant	7/7	ENST00000314485.12	NP_443100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF8	ENST00000314485	c.*30G>A		3_prime_UTR_variant	7/7	1	NM_052868.6	ENSP00000316664.7
IGSF8	ENST00000368086	c.*53G>A		3_prime_UTR_variant	7/7	1		ENSP00000357065.1
IGSF8	ENST00000614243	c.*30G>A		3_prime_UTR_variant	8/8	1		ENSP00000477565.1

Frequencies

GnomAD3 genomes AF: 0.0993 AC: 15076 AN: 151858 Hom.: 999 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.0953

GnomAD4 exome AF: 0.119 AC: 45669 AN: 382818 Hom.: 3129 Cov.: 0 AF XY: 0.118 AC XY: 23705 AN XY: 201038

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0429

Gnomad4 SAS exome AF: 0.0780

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.0993 AC: 15087 AN: 151976 Hom.: 1001 Cov.: 32 AF XY: 0.101 AC XY: 7473 AN XY: 74264

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.0709

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.0962

Alfa AF: 0.121 Hom.: 484

Bravo AF: 0.0942

Asia WGS AF: 0.0850 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1131891; hg19: chr1-160061384;