chr2-43812736-A-C

Position:

• chr2-43812736-A-C

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.*380T>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 0.415 in 197,730 control chromosomes in the GnomAD database, including 19,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16293 hom., cov: 32)
  • Exomes 𝑓: 0.34 (3060 hom.)
• Consequence: ABCG5 NM_022436.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.67

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=-0.94).
• BP6: Variant 2-43812736-A-C is Benign according to our data. Variant chr2-43812736-A-C is described in ClinVar as [Benign]. Clinvar id is 336031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-43812736-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG5	NM_022436.3	c.*380T>G		3_prime_UTR_variant	13/13	ENST00000405322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG5	ENST00000405322.8	c.*380T>G		3_prime_UTR_variant	13/13	1	NM_022436.3	P1
ABCG5	ENST00000486512.5	n.2857T>G		non_coding_transcript_exon_variant	9/9	1
ABCG5	ENST00000644754.1	n.2720T>G		non_coding_transcript_exon_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66283 AN: 151930 Hom.: 16244 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.344 AC: 15701 AN: 45682 Hom.: 3060 Cov.: 0 AF XY: 0.351 AC XY: 8254 AN XY: 23500

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.437 AC: 66382 AN: 152048 Hom.: 16293 Cov.: 32 AF XY: 0.435 AC XY: 32313 AN XY: 74308

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.423

Alfa AF: 0.350 Hom.: 12685

Bravo AF: 0.455

Asia WGS AF: 0.372 AC: 1296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 29066094) -

Sitosterolemia 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.050
DANN	Benign	0.46

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: rs2278356; hg19: chr2-44039875;