19-44913034-C-T

Variant names:

• chr19-44913034-C-T
• rs59325138
• ENST00000623895.1:n.3660C>T

Variant summary

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

The ENST00000623895.1(ENSG00000280087):​n.3660C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,028 control chromosomes in the GnomAD database, including 9,788 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 0.35 (9784 hom., cov: 32)
  • Exomes 𝑓: 0.44 (4 hom.)
• Consequence: ENSG00000280087 ENST00000623895.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• Publications: 29 publications found

Genes affected

ENSG00000280087 (HGNC:):

APOC1 (HGNC:607): (apolipoprotein C1) This gene encodes a member of the apolipoprotein C1 family. This gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. The encoded protein plays a central role in high density lipoprotein (HDL) and very low density lipoprotein (VLDL) metabolism. This protein has also been shown to inhibit cholesteryl ester transfer protein in plasma. A pseudogene of this gene is located 4 kb downstream in the same orientation, on the same chromosome. This gene is mapped to chromosome 19, where it resides within a apolipoprotein gene cluster. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000623895.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000280087	ENST00000623895.1	TSL:6	n.3660C>T		non_coding_transcript_exon	Exon 1 of 1
	APOC1	ENST00000876409.1		c.-482C>T		upstream_gene	N/A	ENSP00000546468.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53054 AN: 151856 Hom.: 9786 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.444 AC: 24 AN: 54 Hom.: 4 Cov.: 0 AF XY: 0.500 AC XY: 21 AN XY: 42

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.447 AC: 17 AN: 38

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.349 AC: 53073 AN: 151974 Hom.: 9784 Cov.: 32 AF XY: 0.350 AC XY: 26002 AN XY: 74278

African (AFR) AF: 0.253 AC: 10480 AN: 41484

American (AMR) AF: 0.305 AC: 4652 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3466

East Asian (EAS) AF: 0.211 AC: 1087 AN: 5144

South Asian (SAS) AF: 0.292 AC: 1409 AN: 4826

European-Finnish (FIN) AF: 0.489 AC: 5162 AN: 10564

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27648 AN: 67904

Other (OTH) AF: 0.372 AC: 784 AN: 2110

Alfa AF: 0.322 Hom.: 3604

Bravo AF: 0.333

Asia WGS AF: 0.235 AC: 818 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.017
DANN	Benign	0.69
PhyloP100		-3.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs59325138;

hg19: chr19-45416291;