rs10491170

chr17-67085903-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.5494+926A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,150 control chromosomes in the GnomAD database, including 4,536 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 0.24 (4536 hom., cov: 32)
• Consequence: HELZ NM_014877.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HELZ	NM_014877.4	c.5494+926A>G		intron_variant		ENST00000358691.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HELZ	ENST00000358691.10	c.5494+926A>G		intron_variant		1	NM_014877.4	P3
HELZ	ENST00000580168.5	c.5497+926A>G		intron_variant		1		A1
HELZ	ENST00000579953.5	c.*2161+926A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36932 AN: 152034 Hom.: 4537 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.243 AC: 36944 AN: 152150 Hom.: 4536 Cov.: 32 AF XY: 0.245 AC XY: 18208 AN XY: 74392

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.242

Alfa AF: 0.231 Hom.: 1435

Bravo AF: 0.239

Asia WGS AF: 0.198 AC: 689 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.11
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: rs10491170; hg19: chr17-65082019;