chr7-128455825-C-G

Variant names:

• chr7-128455825-C-G
• rs2288555
• NM_013332.4:c.-267C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013332.4(HILPDA):​c.-267C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 455,388 control chromosomes in the GnomAD database, including 1,581 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 0.064 (566 hom., cov: 33)
  • Exomes 𝑓: 0.058 (1015 hom.)
• Consequence: HILPDA NM_013332.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852
• Publications: 2 publications found

Genes affected

HILPDA (HGNC:28859): (hypoxia inducible lipid droplet associated) Enables signaling receptor binding activity. Involved in several processes, including autocrine signaling; cellular response to hypoxia; and positive regulation of lipid storage. Located in several cellular components, including cell surface; lipid droplet; and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000273184 (HGNC:):

HILPDA-AS1 (HGNC:55641): (HILPDA antisense RNA 1)

EFCAB3P1 (HGNC:56232): (EFCAB3 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013332.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HILPDA	NM_013332.4	MANE Select	c.-267C>G		upstream_gene	N/A	NP_037464.1	Q9Y5L2
	HILPDA	NM_001098786.2		c.-153C>G		upstream_gene	N/A	NP_001092256.1	Q9Y5L2
	EFCAB3P1	NR_190218.1		n.-53C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HILPDA	ENST00000257696.5	TSL:1 MANE Select	c.-267C>G		upstream_gene	N/A	ENSP00000257696.4	Q9Y5L2
	HILPDA	ENST00000435296.2	TSL:2	c.-153C>G		upstream_gene	N/A	ENSP00000388871.2	Q9Y5L2
	HILPDA	ENST00000916177.1		c.-260C>G		upstream_gene	N/A	ENSP00000586236.1

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9777 AN: 152154 Hom.: 567 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.0613

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.00461

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0618

GnomAD2 exomes AF: 0.0681 AC: 9096 AN: 133494 AF XY: 0.0711

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0589

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.00549

Gnomad NFE exome AF: 0.0268

Gnomad OTH exome AF: 0.0555

GnomAD4 exome AF: 0.0575 AC: 17434 AN: 303118 Hom.: 1015 Cov.: 0 AF XY: 0.0640 AC XY: 11050 AN XY: 172600

African (AFR) AF: 0.118 AC: 1006 AN: 8554

American (AMR) AF: 0.0339 AC: 924 AN: 27234

Ashkenazi Jewish (ASJ) AF: 0.0590 AC: 632 AN: 10714

East Asian (EAS) AF: 0.226 AC: 2070 AN: 9168

South Asian (SAS) AF: 0.131 AC: 7807 AN: 59562

European-Finnish (FIN) AF: 0.00660 AC: 84 AN: 12720

Middle Eastern (MID) AF: 0.0679 AC: 162 AN: 2386

European-Non Finnish (NFE) AF: 0.0250 AC: 3973 AN: 158610

Other (OTH) AF: 0.0548 AC: 776 AN: 14170

GnomAD4 genome AF: 0.0643 AC: 9784 AN: 152270 Hom.: 566 Cov.: 33 AF XY: 0.0652 AC XY: 4857 AN XY: 74446

African (AFR) AF: 0.121 AC: 5041 AN: 41548

American (AMR) AF: 0.0435 AC: 665 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0613 AC: 213 AN: 3472

East Asian (EAS) AF: 0.226 AC: 1168 AN: 5168

South Asian (SAS) AF: 0.138 AC: 666 AN: 4828

European-Finnish (FIN) AF: 0.00461 AC: 49 AN: 10624

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0269 AC: 1828 AN: 68018

Other (OTH) AF: 0.0626 AC: 132 AN: 2110

Alfa AF: 0.0219 Hom.: 17

Bravo AF: 0.0682

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.2
DANN	Benign	0.75
PhyloP100		-0.85
PromoterAI		0.059	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2288555; hg19: chr7-128095879; COSMIC: COSV57556118;