17-55265559-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002126.5(HLF):c.75G>A(p.Leu25=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.52

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 858 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLF	NM_002126.5	c.75G>A	p.Leu25=	synonymous_variant	1/4	ENST00000226067.10
HLF	XM_005257269.3	c.75G>A	p.Leu25=	synonymous_variant	1/4
HLF	XR_002957996.2	n.600G>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLF	ENST00000226067.10	c.75G>A	p.Leu25=	synonymous_variant	1/4	1	NM_002126.5	P1

Frequencies

GnomAD3 genomes AF: 0.00564 AC: 858 AN: 152118 Hom.: 5 Cov.: 32

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.: 5 AF XY: 0.00558 AC XY: 738 AN XY: 132372

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.: 50 Cov.: 30 AF XY: 0.00677 AC XY: 4903 AN XY: 724352

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.: 5 Cov.: 32 AF XY: 0.00547 AC XY: 407 AN XY: 74422

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.: 2

Bravo AF: 0.00568

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	15
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

Other links and lift over

dbSNP: rs140492413; hg19: chr17-53342920;