12-66302630-C-T

Variant names:

• chr12-66302630-C-T
• rs3741604
• NM_001370285.1:c.27C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001370285.1(HELB):​c.27C>T​(p.Arg9Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,336 control chromosomes in the GnomAD database, including 197,414 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 0.40 (13991 hom., cov: 32)
  • Exomes 𝑓: 0.49 (183423 hom.)
• Consequence: HELB NM_001370285.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 28 publications found

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-2.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELB	NM_001370285.1	c.27C>T	p.Arg9Arg	synonymous_variant	Exon 1 of 13	ENST00000247815.9	NP_001357214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELB	ENST00000247815.9	c.27C>T	p.Arg9Arg	synonymous_variant	Exon 1 of 13	1	NM_001370285.1	ENSP00000247815.5
HELB	ENST00000440906.6	n.27C>T		non_coding_transcript_exon_variant	Exon 1 of 12	1		ENSP00000396955.2
HELB	ENST00000542394.5	n.27C>T		non_coding_transcript_exon_variant	Exon 1 of 13	1		ENSP00000439617.1
HELB	ENST00000545134.1	n.27C>T		non_coding_transcript_exon_variant	Exon 1 of 14	2		ENSP00000443287.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61044 AN: 152006 Hom.: 13998 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.453

GnomAD2 exomes AF: 0.430 AC: 108078 AN: 251192 AF XY: 0.444

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.317

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.195

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.527

Gnomad OTH exome AF: 0.475

GnomAD4 exome AF: 0.493 AC: 720130 AN: 1461212 Hom.: 183423 Cov.: 47 AF XY: 0.493 AC XY: 358310 AN XY: 726854

African (AFR) AF: 0.198 AC: 6638 AN: 33468

American (AMR) AF: 0.327 AC: 14616 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 15335 AN: 26124

East Asian (EAS) AF: 0.205 AC: 8117 AN: 39682

South Asian (SAS) AF: 0.426 AC: 36721 AN: 86238

European-Finnish (FIN) AF: 0.394 AC: 21016 AN: 53390

Middle Eastern (MID) AF: 0.573 AC: 3307 AN: 5768

European-Non Finnish (NFE) AF: 0.527 AC: 585884 AN: 1111466

Other (OTH) AF: 0.472 AC: 28496 AN: 60364

GnomAD4 genome AF: 0.401 AC: 61033 AN: 152124 Hom.: 13991 Cov.: 32 AF XY: 0.395 AC XY: 29367 AN XY: 74378

African (AFR) AF: 0.203 AC: 8430 AN: 41514

American (AMR) AF: 0.389 AC: 5946 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2043 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1002 AN: 5176

South Asian (SAS) AF: 0.407 AC: 1959 AN: 4818

European-Finnish (FIN) AF: 0.390 AC: 4125 AN: 10572

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35878 AN: 67958

Other (OTH) AF: 0.454 AC: 957 AN: 2110

Alfa AF: 0.508 Hom.: 29323

Bravo AF: 0.394

Asia WGS AF: 0.307 AC: 1066 AN: 3478

EpiCase AF: 0.548

EpiControl AF: 0.552

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.0
DANN	Benign	0.76
PhyloP100		-2.3
PromoterAI		-0.00010	Neutral
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: rs3741604; hg19: chr12-66696410; COSMIC: COSV56072956;