15-74174979-C-T

Variant names:

• chr15-74174979-C-T
• rs991366708
• NM_005545.4:c.121C>T

Variant summary

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

The NM_005545.4(ISLR):​c.121C>T​(p.Leu41Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000205 in 1,461,126 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ISLR NM_005545.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93
• 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: 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 (BayesDel_noAF=-0.55).

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.121C>T	p.Leu41Leu	synonymous	Exon 2 of 2	NP_005536.1	O14498
	ISLR	NM_201526.2		c.121C>T	p.Leu41Leu	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.121C>T	p.Leu41Leu	synonymous	Exon 2 of 2	ENSP00000249842.3	O14498
	ISLR	ENST00000395118.1	TSL:1	c.121C>T	p.Leu41Leu	synonymous	Exon 2 of 2	ENSP00000378550.1	O14498
	ISLR	ENST00000879093.1		c.121C>T	p.Leu41Leu	synonymous	Exon 2 of 2	ENSP00000549152.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461126 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726852

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53186

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111818

Other (OTH) AF: 0.0000166 AC: 1 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.5
DANN	Benign	0.83
PhyloP100		4.9
PromoterAI		-0.0096	Neutral
Mutation Taster		=88/12	polymorphism

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: rs991366708; hg19: chr15-74467320;