1-160092510-C-A

Variant names:

• chr1-160092510-C-A
• rs561389264
• NM_052868.6:c.1498G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052868.6(IGSF8):​c.1498G>T​(p.Val500Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V500I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: IGSF8 NM_052868.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041776717).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052868.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF8	NM_052868.6	MANE Select	c.1498G>T	p.Val500Leu	missense	Exon 5 of 7	NP_443100.1	Q969P0-1
	IGSF8	NM_001206665.2		c.1498G>T	p.Val500Leu	missense	Exon 6 of 8	NP_001193594.1	Q969P0-1
	IGSF8	NM_001320247.2		c.1498G>T	p.Val500Leu	missense	Exon 5 of 7	NP_001307176.1	Q969P0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF8	ENST00000314485.12	TSL:1 MANE Select	c.1498G>T	p.Val500Leu	missense	Exon 5 of 7	ENSP00000316664.7	Q969P0-1
	IGSF8	ENST00000368086.5	TSL:1	c.1498G>T	p.Val500Leu	missense	Exon 5 of 7	ENSP00000357065.1	Q969P0-1
	IGSF8	ENST00000614243.4	TSL:1	c.1498G>T	p.Val500Leu	missense	Exon 6 of 8	ENSP00000477565.1	Q969P0-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152256 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247364 AF XY: 0.0000223

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460976 Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11 AN XY: 726794

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111776

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.2
DANN	Benign	0.89
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-0.78
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.017
Sift	Benign	0.65	T
Sift4G	Benign	0.70	T
Polyphen		0.0030	B
Vest4		0.17
MutPred		0.50		Loss of loop (P = 0.0986)
MVP		0.055
MPC		0.14
ClinPred		0.017	T
GERP RS		0.086
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.30
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs561389264; hg19: chr1-160062300;