19-4502189-T-C

Position:

• chr19-4502189-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001001520.3(HDGFL2):​c.*179T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 678,242 control chromosomes in the GnomAD database, including 93,181 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 0.51 (19914 hom., cov: 32)
  • Exomes 𝑓: 0.52 (73267 hom.)
• Consequence: HDGFL2 NM_001001520.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91

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]

PLIN4 (HGNC:29393): (perilipin 4) Members of the perilipin family, such as PLIN4, coat intracellular lipid storage droplets (Wolins et al., 2003 [PubMed 12840023]).[supplied by OMIM, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDGFL2	NM_001001520.3	c.*179T>C		3_prime_UTR_variant	16/16	ENST00000616600.5	NP_001001520.1
PLIN4	NM_001367868.2	c.*2270A>G		downstream_gene_variant		ENST00000301286.5	NP_001354797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDGFL2	ENST00000616600.5	c.*179T>C		3_prime_UTR_variant	16/16	1	NM_001001520.3	ENSP00000483345.1
PLIN4	ENST00000301286.5	c.*2270A>G		downstream_gene_variant		5	NM_001367868.2	ENSP00000301286.4

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76853 AN: 151870 Hom.: 19901 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.482

GnomAD3 exomes AF: 0.515 AC: 58539 AN: 113682 Hom.: 15591 AF XY: 0.509 AC XY: 31528 AN XY: 61926

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.585

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.347

Gnomad SAS exome AF: 0.404

Gnomad FIN exome AF: 0.530

Gnomad NFE exome AF: 0.561

Gnomad OTH exome AF: 0.524

GnomAD4 exome AF: 0.521 AC: 274098 AN: 526256 Hom.: 73267 Cov.: 4 AF XY: 0.514 AC XY: 147017 AN XY: 285766

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.580

Gnomad4 ASJ exome AF: 0.551

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.506 AC: 76905 AN: 151986 Hom.: 19914 Cov.: 32 AF XY: 0.504 AC XY: 37477 AN XY: 74292

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.481

Alfa AF: 0.541 Hom.: 36247

Bravo AF: 0.508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.91

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: rs8887; hg19: chr19-4502201;