19-4502189-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001348169.2(HDGFL2):​c.*179T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000251 in 678,536 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000095 (0 hom.)
• Consequence: HDGFL2 NM_001348169.2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348169.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDGFL2	NM_001001520.3	MANE Select	c.*179T>G		3_prime_UTR	Exon 16 of 16	NP_001001520.1
	HDGFL2	NM_001348169.2		c.*179T>G		3_prime_UTR	Exon 16 of 16	NP_001335098.1
	HDGFL2	NM_032631.4		c.*179T>G		3_prime_UTR	Exon 16 of 16	NP_116020.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDGFL2	ENST00000616600.5	TSL:1 MANE Select	c.*179T>G		3_prime_UTR	Exon 16 of 16	ENSP00000483345.1
	HDGFL2	ENST00000621835.4	TSL:1	c.*179T>G		3_prime_UTR	Exon 16 of 16	ENSP00000483702.1
	PLIN4	ENST00000901551.1		c.*2270A>C		3_prime_UTR	Exon 8 of 8	ENSP00000571610.1

Frequencies

GnomAD3 genomes AF: 0.0000790 AC: 12 AN: 151916 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000176 AC: 2 AN: 113682 AF XY: 0.0000323

Gnomad AFR exome AF: 0.000337

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000949 AC: 5 AN: 526620 Hom.: 0 Cov.: 4 AF XY: 0.0000175 AC XY: 5 AN XY: 285920

African (AFR) AF: 0.000289 AC: 4 AN: 13828

American (AMR) AF: 0.00 AC: 0 AN: 26528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19410

East Asian (EAS) AF: 0.00 AC: 0 AN: 31780

South Asian (SAS) AF: 0.00 AC: 0 AN: 56560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3974

European-Non Finnish (NFE) AF: 0.00000321 AC: 1 AN: 311788

Other (OTH) AF: 0.00 AC: 0 AN: 29568

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151916 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74186

African (AFR) AF: 0.000290 AC: 12 AN: 41346

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 84574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		2.9

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;