rs7590705

Positions:

• chr2-127467652-A-G

Variant summary

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

The ENST00000454503.6(ENSG00000231731):​n.76A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,528 control chromosomes in the GnomAD database, including 24,981 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 0.56 (24960 hom., cov: 31)
  • Exomes 𝑓: 0.53 (21 hom.)
• Consequence: ENSG00000231731 ENST00000454503.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

Genes affected

ENSG00000231731 (HGNC:):

IWS1 (HGNC:25467): (interacts with SUPT6H, CTD assembly factor 1) Involved in regulation of histone modification; regulation of mRNA export from nucleus; and regulation of mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.127467652A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000231731	ENST00000454503.6	n.76A>G		non_coding_transcript_exon_variant	1/3	2
ENSG00000231731	ENST00000626634.2	n.68A>G		non_coding_transcript_exon_variant	1/5	5
IWS1	ENST00000412979.1	n.*248+2334T>C		intron_variant		3		ENSP00000396710.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84364 AN: 151282 Hom.: 24911 Cov.: 31

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.563

GnomAD4 exome AF: 0.531 AC: 68 AN: 128 Hom.: 21 Cov.: 0 AF XY: 0.560 AC XY: 47 AN XY: 84

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.558 AC: 84473 AN: 151400 Hom.: 24960 Cov.: 31 AF XY: 0.556 AC XY: 41171 AN XY: 74022

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.569

Alfa AF: 0.506 Hom.: 28460

Bravo AF: 0.556

Asia WGS AF: 0.547 AC: 1905 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7590705; hg19: chr2-128225228;