rs1407335

chr20-13242211-A-Cchr20-13242211-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.138+20297A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,924 control chromosomes in the GnomAD database, including 9,348 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 0.34 (9348 hom., cov: 32)
• Consequence: ISM1 NM_080826.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISM1	NM_080826.2	c.138+20297A>C		intron_variant		ENST00000262487.5
ISM1	XM_017027680.2	c.138+20297A>C		intron_variant
TASP1	XR_007067463.1	n.25341T>G		non_coding_transcript_exon_variant	15/15
TASP1	XR_001754319.3	n.1369+73759T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISM1	ENST00000262487.5	c.138+20297A>C		intron_variant		5	NM_080826.2	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51706 AN: 151806 Hom.: 9326 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.341 AC: 51776 AN: 151924 Hom.: 9348 Cov.: 32 AF XY: 0.344 AC XY: 25529 AN XY: 74246

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.334

Alfa AF: 0.276 Hom.: 3363

Bravo AF: 0.350

Asia WGS AF: 0.404 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.48
Dann	Benign	0.54

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: rs1407335; hg19: chr20-13222858;