dbSNP rs142161059: HELB:p.Pro6Arg (chr12-66302620-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2BP4_StrongBS2

The NM_001370285.1(HELB):c.17C>G(p.Pro6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

HELB
NM_001370285.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.64

Publications

0 publications found

Variant links:

Genes affected

HELB (HGNC:17196): (DNA helicase B) This gene encodes a DNA-dependent ATPase which catalyzes the unwinding of DNA necessary for DNA replication, repair, recombination, and transcription. This gene is thought to function specifically during the S phase entry of the cell cycle. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

HELB Gene-Disease associations (from GenCC):

familial ovarian carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

HELB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029571086).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370285.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HELB	NM_001370285.1	MANE Select	c.17C>G	p.Pro6Arg	missense	Exon 1 of 13	NP_001357214.1	Q8NG08-1
HELB	NM_033647.5		c.17C>G	p.Pro6Arg	missense	Exon 1 of 14	NP_387467.2
HELB	NR_135080.2		n.128C>G		non_coding_transcript_exon	Exon 1 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HELB	ENST00000247815.9	TSL:1 MANE Select	c.17C>G	p.Pro6Arg	missense	Exon 1 of 13	ENSP00000247815.5	Q8NG08-1
HELB	ENST00000440906.6	TSL:1	n.17C>G		non_coding_transcript_exon	Exon 1 of 12	ENSP00000396955.2	Q8NG08-2
HELB	ENST00000542394.5	TSL:1	n.17C>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000439617.1	F5H1I4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251166

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461584

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727072

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000112

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111780

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.013

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.00036

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0029

M_CAP

Benign

0.0042

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.55

PhyloP100

-1.6

PrimateAI

Benign

0.23

PROVEAN

Benign

0.50

REVEL

Benign

0.0040

Sift

Benign

0.81

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.033

MutPred

0.31

Gain of MoRF binding (P = 2e-04)

MVP

0.055

MPC

0.17

ClinPred

0.041

GERP RS

-1.0

PromoterAI

0.0099

Neutral

(source)

Varity_R

0.021

gMVP

0.22

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over