2-43820391-C-T

Position:

• chr2-43820391-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022436.3(ABCG5):​c.1464-291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,062 control chromosomes in the GnomAD database, including 6,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (6956 hom., cov: 32)
• Consequence: ABCG5 NM_022436.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.371

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-43820391-C-T is Benign according to our data. Variant chr2-43820391-C-T is described in ClinVar as [Benign]. Clinvar id is 1293774.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG5	NM_022436.3	c.1464-291G>A		intron_variant		ENST00000405322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG5	ENST00000405322.8	c.1464-291G>A		intron_variant		1	NM_022436.3	P1
ABCG5	ENST00000486512.5	n.1985-291G>A		intron_variant, non_coding_transcript_variant		1
ABCG5	ENST00000409962.1	n.1747-291G>A		intron_variant, non_coding_transcript_variant		2
ABCG5	ENST00000644754.1	n.1848-291G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36498 AN: 151944 Hom.: 6930 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.241 AC: 36580 AN: 152062 Hom.: 6956 Cov.: 32 AF XY: 0.238 AC XY: 17654 AN XY: 74326

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0567

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.199

Alfa AF: 0.129 Hom.: 2548

Bravo AF: 0.265

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.47

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: rs4148189; hg19: chr2-44047530;