rs79206759

Variant names:

• chr15-74174987-C-T
• rs79206759
• NM_005545.4:c.129C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005545.4(ISLR):​c.129C>T​(p.Ser43Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,612,966 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (103 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (96 hom.)
• Consequence: ISLR NM_005545.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38
• Publications: 1 publications found

Genes affected

ISLR (HGNC:6133): (immunoglobulin superfamily containing leucine rich repeat) Predicted to be involved in cell adhesion. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261543 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-74174987-C-T is Benign according to our data. Variant chr15-74174987-C-T is described in ClinVar as Benign. ClinVar VariationId is 779898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005545.4. 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
	ISLR	NM_005545.4	MANE Select	c.129C>T	p.Ser43Ser	synonymous	Exon 2 of 2	NP_005536.1	O14498
	ISLR	NM_201526.2		c.129C>T	p.Ser43Ser	synonymous	Exon 2 of 2	NP_958934.1	O14498

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISLR	ENST00000249842.8	TSL:1 MANE Select	c.129C>T	p.Ser43Ser	synonymous	Exon 2 of 2	ENSP00000249842.3	O14498
	ISLR	ENST00000395118.1	TSL:1	c.129C>T	p.Ser43Ser	synonymous	Exon 2 of 2	ENSP00000378550.1	O14498
	ISLR	ENST00000879093.1		c.129C>T	p.Ser43Ser	synonymous	Exon 2 of 2	ENSP00000549152.1

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2947 AN: 152074 Hom.: 104 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00739

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: 0.000147

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00519 AC: 1297 AN: 249680 AF XY: 0.00368

Gnomad AFR exome AF: 0.0711

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00202 AC: 2948 AN: 1460774 Hom.: 96 Cov.: 29 AF XY: 0.00172 AC XY: 1249 AN XY: 726702

African (AFR) AF: 0.0714 AC: 2386 AN: 33406

American (AMR) AF: 0.00371 AC: 165 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000929 AC: 8 AN: 86102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53172

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5764

European-Non Finnish (NFE) AF: 0.000116 AC: 129 AN: 1111752

Other (OTH) AF: 0.00408 AC: 246 AN: 60344

GnomAD4 genome AF: 0.0194 AC: 2955 AN: 152192 Hom.: 103 Cov.: 32 AF XY: 0.0189 AC XY: 1403 AN XY: 74404

African (AFR) AF: 0.0675 AC: 2804 AN: 41530

American (AMR) AF: 0.00738 AC: 113 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67986

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.00860 Hom.: 31

Bravo AF: 0.0226

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.82
PhyloP100		-1.4
PromoterAI		-0.00060	Neutral
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: rs79206759; hg19: chr15-74467328;