15-74175392-C-T

Variant names:

• chr15-74175392-C-T
• rs114338290
• NM_005545.4:c.534C>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.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
• Publications: 0 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=-0.71).
• BP6: Variant 15-74175392-C-T is Benign according to our data. Variant chr15-74175392-C-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.534C>T	p.Asn178Asn	synonymous	Exon 2 of 2	NP_005536.1	O14498
	ISLR	NM_201526.2		c.534C>T	p.Asn178Asn	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.534C>T	p.Asn178Asn	synonymous	Exon 2 of 2	ENSP00000249842.3	O14498
	ISLR	ENST00000395118.1	TSL:1	c.534C>T	p.Asn178Asn	synonymous	Exon 2 of 2	ENSP00000378550.1	O14498
	ISLR	ENST00000879093.1		c.534C>T	p.Asn178Asn	synonymous	Exon 2 of 2	ENSP00000549152.1

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

GnomAD2 exomes AF: 0.00466 AC: 1159 AN: 248808 AF XY: 0.00340

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 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

African (AFR) AF: 0.0613 AC: 2051 AN: 33476

American (AMR) AF: 0.00412 AC: 184 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86206

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51328

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.000187 AC: 208 AN: 1111888

Other (OTH) AF: 0.00459 AC: 277 AN: 60370

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

African (AFR) AF: 0.0617 AC: 2564 AN: 41574

American (AMR) AF: 0.00588 AC: 90 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

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

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68032

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.00746 Hom.: 21

Bravo AF: 0.0195

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000771

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	-0.71
CADD	Benign	2.7
DANN	Benign	0.91
PhyloP100		-0.24
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: rs114338290; hg19: chr15-74467733;