19-4500193-A-G

Position:

• chr19-4500193-A-G

Variant summary

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

The ENST00000616600.5(HDGFL2):​c.1789+489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,266 control chromosomes in the GnomAD database, including 49,364 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 0.80 (49364 hom., cov: 35)
• Consequence: HDGFL2 ENST00000616600.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

Genes affected

HDGFL2 (HGNC:14680): (HDGF like 2) This gene encodes a member of the hepatoma-derived growth factor (HDGF) family. The protein includes an N-terminal PWWP domain that binds to methyl-lysine-containing histones, with specific binding of this protein to tri-methylated lysines 36 and 79 of histone H3, and di- and tri-methylated lysine 20 of histone H4. The protein functions in LEDGF/p75-independent HIV-1 replication by determining HIV-1 integration site selection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDGFL2	NM_001001520.3	c.1789+489A>G		intron_variant		ENST00000616600.5	NP_001001520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDGFL2	ENST00000616600.5	c.1789+489A>G		intron_variant		1	NM_001001520.3	ENSP00000483345	P5

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121577 AN: 152148 Hom.: 49345 Cov.: 35

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.800

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

GnomAD4 genome AF: 0.799 AC: 121649 AN: 152266 Hom.: 49364 Cov.: 35 AF XY: 0.800 AC XY: 59532 AN XY: 74446

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.804

Alfa AF: 0.843 Hom.: 53244

Bravo AF: 0.795

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.34

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: rs10406797; hg19: chr19-4500205;