NM_014877.4:c.5494+926A>G

Variant names:

• chr17-67085903-T-C
• rs10491170
• NM_014877.4:c.5494+926A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HELZ	NM_014877.4	c.5494+926A>G		intron_variant	Intron 32 of 32	ENST00000358691.10	NP_055692.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELZ	ENST00000358691.10	c.5494+926A>G		intron_variant	Intron 32 of 32	1	NM_014877.4	ENSP00000351524.5
HELZ	ENST00000580168.5	c.5497+926A>G		intron_variant	Intron 32 of 32	1		ENSP00000464512.1
HELZ	ENST00000579953.5	n.*2161+926A>G		intron_variant	Intron 30 of 30	2		ENSP00000463727.1

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

African (AFR) AF: 0.270 AC: 11194 AN: 41488

American (AMR) AF: 0.221 AC: 3384 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5174

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4824

European-Finnish (FIN) AF: 0.294 AC: 3115 AN: 10586

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15436 AN: 67992

Other (OTH) AF: 0.242 AC: 513 AN: 2116

Alfa AF: 0.234 Hom.: 1811

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10491170; hg19: chr17-65082019;