rs7224610

Variant names:

• chr17-55287427-C-A
• rs7224610
• NM_002126.5:c.451+19341C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-55287427-C-A
• chr17-55287427-C-G
• chr17-55287427-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HLF	NM_002126.5	c.451+19341C>A		intron_variant	Intron 2 of 3	ENST00000226067.10	NP_002117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLF	ENST00000226067.10	c.451+19341C>A		intron_variant	Intron 2 of 3	1	NM_002126.5	ENSP00000226067.5

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

African (AFR) AF: 0.905 AC: 37559 AN: 41514

American (AMR) AF: 0.663 AC: 10146 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3470

East Asian (EAS) AF: 0.855 AC: 4429 AN: 5178

South Asian (SAS) AF: 0.723 AC: 3482 AN: 4818

European-Finnish (FIN) AF: 0.591 AC: 6224 AN: 10536

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.589 AC: 40064 AN: 67986

Other (OTH) AF: 0.667 AC: 1404 AN: 2106

Alfa AF: 0.625 Hom.: 89977

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
PhyloP100		0.85
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: rs7224610; hg19: chr17-53364788;