rs17191018

Positions:

• chr20-13298549-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080826.2(ISM1):​c.878-393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 152,308 control chromosomes in the GnomAD database, including 258 homozygotes. 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: 𝑓 0.050 (258 hom., cov: 33)
• Consequence: ISM1 NM_080826.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

Genes affected

ISM1 (HGNC:16213): (isthmin 1) Predicted to be involved in negative regulation of angiogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

TASP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISM1	NM_080826.2	c.878-393A>G		intron_variant		ENST00000262487.5
ISM1	XM_017027680.2	c.877+6086A>G		intron_variant
TASP1	XR_001754319.3	n.1369+17421T>C		intron_variant, non_coding_transcript_variant
TASP1	XR_007067463.1	n.1369+17421T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISM1	ENST00000262487.5	c.878-393A>G		intron_variant		5	NM_080826.2	P1

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7548 AN: 152190 Hom.: 258 Cov.: 33

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0598

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0496 AC: 7550 AN: 152308 Hom.: 258 Cov.: 33 AF XY: 0.0513 AC XY: 3818 AN XY: 74474

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.0913

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0485

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0467 Hom.: 29

Bravo AF: 0.0486

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.42

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: rs17191018; hg19: chr20-13279196;