rs7224610

chr17-55287427-C-Achr17-55287427-C-Gchr17-55287427-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002126.5(HLF):c.451+19341C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,104 control chromosomes in the GnomAD database, including 38,246 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 0.70 (38246 hom., cov: 33)
• Consequence: HLF NM_002126.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLF	NM_002126.5	c.451+19341C>A		intron_variant		ENST00000226067.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLF	ENST00000226067.10	c.451+19341C>A		intron_variant		1	NM_002126.5	P1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105686 AN: 151988 Hom.: 38200 Cov.: 33

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.695 AC: 105788 AN: 152104 Hom.: 38246 Cov.: 33 AF XY: 0.697 AC XY: 51797 AN XY: 74352

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.667

Alfa AF: 0.597 Hom.: 34760

Bravo AF: 0.709

Asia WGS AF: 0.785 AC: 2729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.3
Dann	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs7224610; hg19: chr17-53364788;