chr2-43812594-C-T

Position:

• chr2-43812594-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022436.3(ABCG5):​c.*522G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 169,228 control chromosomes in the GnomAD database, including 2,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2607 hom., cov: 31)
  • Exomes 𝑓: 0.15 (251 hom.)
• Consequence: ABCG5 NM_022436.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.323

Genes affected

ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

DYNC2LI1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-43812594-C-T is Benign according to our data. Variant chr2-43812594-C-T is described in ClinVar as [Benign]. Clinvar id is 336027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG5	NM_022436.3	c.*522G>A		3_prime_UTR_variant	13/13	ENST00000405322.8	NP_071881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG5	ENST00000405322.8	c.*522G>A		3_prime_UTR_variant	13/13	1	NM_022436.3	ENSP00000384513	P1
ABCG5	ENST00000486512.5	n.2999G>A		non_coding_transcript_exon_variant	9/9	1
ABCG5	ENST00000644754.1	n.2862G>A		non_coding_transcript_exon_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27205 AN: 151814 Hom.: 2595 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0199

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.148 AC: 2568 AN: 17296 Hom.: 251 Cov.: 0 AF XY: 0.150 AC XY: 1316 AN XY: 8762

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.0106

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.179 AC: 27253 AN: 151932 Hom.: 2607 Cov.: 31 AF XY: 0.179 AC XY: 13265 AN XY: 74272

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.191

Alfa AF: 0.179 Hom.: 372

Bravo AF: 0.178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Sitosterolemia 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.54

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: rs77105521; hg19: chr2-44039733;