Variant 17-55265559-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002126.5(HLF):c.75G>A(p.Leu25Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00675 in 1,608,052 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 50 hom. )

Consequence

HLF
NM_002126.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.52

Variant links:

Genes affected

HLF (HGNC:4977): (HLF transcription factor, PAR bZIP family member) This gene encodes a member of the proline and acidic-rich (PAR) protein family, a subset of the bZIP transcription factors. The encoded protein forms homodimers or heterodimers with other PAR family members and binds sequence-specific promoter elements to activate transcription. Chromosomal translocations fusing portions of this gene with the E2A gene cause a subset of childhood B-lineage acute lymphoid leukemias. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

HLF links:

HLF (HGNC:):

HLF links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-55265559-G-A is Benign according to our data. Variant chr17-55265559-G-A is described in ClinVar as [Benign]. Clinvar id is 779173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 857 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLF	NM_002126.5 linkuse as main transcript	c.75G>A	p.Leu25Leu	synonymous_variant	1/4	ENST00000226067.10	NP_002117.1	Q16534-1
HLF	XM_005257269.3 linkuse as main transcript	c.75G>A	p.Leu25Leu	synonymous_variant	1/4		XP_005257326.1
HLF	XR_002957996.2 linkuse as main transcript	n.600G>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLF	ENST00000226067.10 linkuse as main transcript	c.75G>A	p.Leu25Leu	synonymous_variant	1/4	1	NM_002126.5	ENSP00000226067.5		Q16534-1

Frequencies

GnomAD3 genomes

AF:

0.00564

AC:

858

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00820

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00552

AC:

1346

AN:

243800

Hom.:

AF XY:

0.00558

AC XY:

738

AN XY:

132372

show subpopulations

Gnomad AFR exome

AF:

0.00170

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00123

Gnomad FIN exome

AF:

0.00295

Gnomad NFE exome

AF:

0.00811

Gnomad OTH exome

AF:

0.00762

GnomAD4 exome

AF:

0.00686

AC:

9991

AN:

1455820

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

4903

AN XY:

724352

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00544

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00164

Gnomad4 FIN exome

AF:

0.00372

Gnomad4 NFE exome

AF:

0.00768

Gnomad4 OTH exome

AF:

0.00718

GnomAD4 genome

AF:

0.00563

AC:

857

AN:

152232

Hom.:

Cov.:

AF XY:

0.00547

AC XY:

407

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00819

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00799

Hom.:

Bravo

AF:

0.00568

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over