19-4502189-T-C

Variant names:

• chr19-4502189-T-C
• rs8887
• NM_001001520.3:c.*179T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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]

PLIN4 Gene-Disease associations (from GenCC):

• vacuolar Neuromyopathy

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HDGFL2	NM_001001520.3	c.*179T>C		3_prime_UTR_variant	Exon 16 of 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 rank	TSL	MANE	Protein	Appris	UniProt
HDGFL2	ENST00000616600.5	c.*179T>C		3_prime_UTR_variant	Exon 16 of 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

GnomAD2 exomes AF: 0.515 AC: 58539 AN: 113682 AF XY: 0.509

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 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

African (AFR) AF: 0.423 AC: 5841 AN: 13816

American (AMR) AF: 0.580 AC: 15364 AN: 26492

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 10683 AN: 19396

East Asian (EAS) AF: 0.322 AC: 10225 AN: 31748

South Asian (SAS) AF: 0.405 AC: 22920 AN: 56544

European-Finnish (FIN) AF: 0.520 AC: 17257 AN: 33158

Middle Eastern (MID) AF: 0.512 AC: 2033 AN: 3970

European-Non Finnish (NFE) AF: 0.559 AC: 174275 AN: 311592

Other (OTH) AF: 0.525 AC: 15500 AN: 29540

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

African (AFR) AF: 0.423 AC: 17517 AN: 41456

American (AMR) AF: 0.552 AC: 8426 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3470

East Asian (EAS) AF: 0.350 AC: 1805 AN: 5162

South Asian (SAS) AF: 0.367 AC: 1774 AN: 4830

European-Finnish (FIN) AF: 0.525 AC: 5538 AN: 10548

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.561 AC: 38084 AN: 67936

Other (OTH) AF: 0.481 AC: 1015 AN: 2108

Alfa AF: 0.539 Hom.: 84574

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
PhyloP100		2.9
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: rs8887; hg19: chr19-4502201;