rs4245786

chr2-43821981-G-Achr2-43821981-G-C

Variant summary

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

The NM_022436.3(ABCG5):c.1463+816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 151,986 control chromosomes in the GnomAD database, including 45,969 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 0.78 (45969 hom., cov: 30)
• Consequence: ABCG5 NM_022436.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG5	NM_022436.3	c.1463+816C>T		intron_variant		ENST00000405322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG5	ENST00000405322.8	c.1463+816C>T		intron_variant		1	NM_022436.3	P1
ABCG5	ENST00000486512.5	n.1984+816C>T		intron_variant, non_coding_transcript_variant		1
ABCG5	ENST00000409962.1	n.1746+816C>T		intron_variant, non_coding_transcript_variant		2
ABCG5	ENST00000644754.1	n.1847+816C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117972 AN: 151868 Hom.: 45927 Cov.: 30

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.777 AC: 118072 AN: 151986 Hom.: 45969 Cov.: 30 AF XY: 0.780 AC XY: 57961 AN XY: 74304

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.775

Alfa AF: 0.765 Hom.: 61373

Bravo AF: 0.772

Asia WGS AF: 0.822 AC: 2859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.9
Dann	Benign	0.80

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: rs4245786; hg19: chr2-44049120;