10-94564394-A-G

Variant names:

• chr10-94564394-A-G
• rs1969815
• NM_018063.5:c.435+1518A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018063.5(HELLS):​c.435+1518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,014 control chromosomes in the GnomAD database, including 11,485 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 0.38 (11485 hom., cov: 32)
• Consequence: HELLS NM_018063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 3 publications found

Genes affected

HELLS (HGNC:4861): (helicase, lymphoid specific) This gene encodes a lymphoid-specific helicase. Other helicases function in processes involving DNA strand separation, including replication, repair, recombination, and transcription. This protein is thought to be involved with cellular proliferation and may play a role in leukemogenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2014]

HELLS Gene-Disease associations (from GenCC):

• immunodeficiency-centromeric instability-facial anomalies syndrome 4

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• immunodeficiency-centromeric instability-facial anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELLS	NM_018063.5	c.435+1518A>G		intron_variant	Intron 6 of 21	ENST00000348459.10	NP_060533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELLS	ENST00000348459.10	c.435+1518A>G		intron_variant	Intron 6 of 21	1	NM_018063.5	ENSP00000239027.7

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57963 AN: 151896 Hom.: 11487 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.381 AC: 57975 AN: 152014 Hom.: 11485 Cov.: 32 AF XY: 0.383 AC XY: 28450 AN XY: 74262

African (AFR) AF: 0.329 AC: 13628 AN: 41464

American (AMR) AF: 0.335 AC: 5119 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1182 AN: 3472

East Asian (EAS) AF: 0.684 AC: 3537 AN: 5174

South Asian (SAS) AF: 0.546 AC: 2624 AN: 4808

European-Finnish (FIN) AF: 0.354 AC: 3728 AN: 10544

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26897 AN: 67980

Other (OTH) AF: 0.372 AC: 785 AN: 2110

Alfa AF: 0.391 Hom.: 33484

Bravo AF: 0.376

Asia WGS AF: 0.586 AC: 2039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		1.7
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: rs1969815; hg19: chr10-96324151;