15-74175392-C-T

Variant names:

• chr15-74175392-C-T
• rs114338290
• NM_005545.4:c.534C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005545.4(ISLR):​c.534C>T​(p.Asn178Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,611,888 control chromosomes in the GnomAD database, including 163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (63 hom.)
• Consequence: ISLR NM_005545.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.240

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 15-74175392-C-T is Benign according to our data. Variant chr15-74175392-C-T is described in ClinVar as [Benign]. Clinvar id is 781311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISLR	NM_005545.4	c.534C>T	p.Asn178Asn	synonymous_variant	Exon 2 of 2	ENST00000249842.8	NP_005536.1
ISLR	NM_201526.2	c.534C>T	p.Asn178Asn	synonymous_variant	Exon 2 of 2		NP_958934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISLR	ENST00000249842.8	c.534C>T	p.Asn178Asn	synonymous_variant	Exon 2 of 2	1	NM_005545.4	ENSP00000249842.3

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2701 AN: 152220 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00466 AC: 1159 AN: 248808 Hom.: 43 AF XY: 0.00340 AC XY: 458 AN XY: 134700

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.0000997

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000982

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.00189 AC: 2752 AN: 1459550 Hom.: 63 Cov.: 30 AF XY: 0.00159 AC XY: 1156 AN XY: 726178

Gnomad4 AFR exome AF: 0.0613

Gnomad4 AMR exome AF: 0.00412

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.0000195

Gnomad4 NFE exome AF: 0.000187

Gnomad4 OTH exome AF: 0.00459

GnomAD4 genome AF: 0.0178 AC: 2713 AN: 152338 Hom.: 100 Cov.: 32 AF XY: 0.0174 AC XY: 1294 AN XY: 74498

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.00588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00739 Hom.: 18

Bravo AF: 0.0195

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.7
DANN	Benign	0.91

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: rs114338290; hg19: chr15-74467733;