chr2-127467652-A-G

Variant names:

• chr2-127467652-A-G
• rs7590705
• ENST00000454503.6:n.76A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000454503.6. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000231731	ENST00000454503.6	TSL:2	n.76A>G		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000231731	ENST00000626634.2	TSL:5	n.68A>G		non_coding_transcript_exon	Exon 1 of 5
	IWS1	ENST00000412979.1	TSL:3	n.*248+2334T>C		intron	N/A	ENSP00000396710.1	H7C0U1

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

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.588 AC: 20 AN: 34

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.471 AC: 32 AN: 68

Other (OTH) AF: 0.667 AC: 8 AN: 12

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

African (AFR) AF: 0.739 AC: 30214 AN: 40864

American (AMR) AF: 0.440 AC: 6711 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1497 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2194 AN: 5166

South Asian (SAS) AF: 0.587 AC: 2833 AN: 4826

European-Finnish (FIN) AF: 0.516 AC: 5448 AN: 10558

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33892 AN: 67958

Other (OTH) AF: 0.569 AC: 1199 AN: 2108

Alfa AF: 0.509 Hom.: 40122

Bravo AF: 0.556

Asia WGS AF: 0.547 AC: 1905 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.36
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs7590705; hg19: chr2-128225228;