rs9332408

chr17-67112871-T-C

Variant summary

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

The NM_014877.4(HELZ):c.3918+1453A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,860 control chromosomes in the GnomAD database, including 19,162 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 0.49 (19162 hom., cov: 32)
• Consequence: HELZ NM_014877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

HELZ (HGNC:16878): (helicase with zinc finger) HELZ is a member of the superfamily I class of RNA helicases. RNA helicases alter the conformation of RNA by unwinding double-stranded regions, thereby altering the biologic activity of the RNA molecule and regulating access to other proteins (Wagner et al., 1999 [PubMed 10471385]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELZ	NM_014877.4	c.3918+1453A>G		intron_variant		ENST00000358691.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELZ	ENST00000358691.10	c.3918+1453A>G		intron_variant		1	NM_014877.4	P3
HELZ	ENST00000580168.5	c.3921+1453A>G		intron_variant		1		A1
HELZ	ENST00000579953.5	c.*585+1453A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74552 AN: 151742 Hom.: 19160 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.491 AC: 74571 AN: 151860 Hom.: 19162 Cov.: 32 AF XY: 0.502 AC XY: 37256 AN XY: 74198

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.491

Alfa AF: 0.483 Hom.: 17705

Bravo AF: 0.488

Asia WGS AF: 0.723 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.66
Dann	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9332408; hg19: chr17-65108987;