rs10439467

Variant names:

• chr2-43821207-C-T
• rs10439467
• NM_022436.3:c.1464-1107G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022436.3(ABCG5):​c.1464-1107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,196 control chromosomes in the GnomAD database, including 576 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 0.074 (576 hom., cov: 32)
• Consequence: ABCG5 NM_022436.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501

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:24595): (dynein cytoplasmic 2 light intermediate chain 1) This gene encodes a protein that is a component of the dynein-2 microtubule motor protein complex that plays a role in the retrograde transport of cargo in primary cilia via the intraflagellar transport system. This gene is ubiquitously expressed and its protein, which localizes to the axoneme and Golgi apparatus, interacts directly with the cytoplasmic dynein 2 heavy chain 1 protein to form part of the multi-protein dynein-2 complex. Mutations in this gene produce defects in the dynein-2 complex which result in several types of ciliopathy including short-rib thoracic dysplasia 15 with polydactyly (SRTD15). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG5	NM_022436.3	c.1464-1107G>A		intron_variant	Intron 10 of 12	ENST00000405322.8	NP_071881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG5	ENST00000405322.8	c.1464-1107G>A		intron_variant	Intron 10 of 12	1	NM_022436.3	ENSP00000384513.2
ABCG5	ENST00000486512.5	n.1985-1107G>A		intron_variant	Intron 6 of 8	1
ABCG5	ENST00000409962.1	n.1747-1107G>A		intron_variant	Intron 6 of 8	2
ABCG5	ENST00000644754.1	n.1848-1107G>A		intron_variant	Intron 7 of 9

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 11319 AN: 152078 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0837

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0705

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

GnomAD4 genome AF: 0.0745 AC: 11336 AN: 152196 Hom.: 576 Cov.: 32 AF XY: 0.0760 AC XY: 5658 AN XY: 74424

Gnomad4 AFR AF: 0.0637

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0837

Gnomad4 EAS AF: 0.0448

Gnomad4 SAS AF: 0.0661

Gnomad4 FIN AF: 0.0629

Gnomad4 NFE AF: 0.0613

Gnomad4 OTH AF: 0.0717

Alfa AF: 0.0900 Hom.: 408

Bravo AF: 0.0851

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.43

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: rs10439467; hg19: chr2-44048346;