chr2-43846517-T-C

Position:

• chr2-43846517-T-C

Variant summary

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

The NM_022437.3(ABCG8):​c.322+206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 700,082 control chromosomes in the GnomAD database, including 1,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (573 hom., cov: 32)
  • Exomes 𝑓: 0.062 (1186 hom.)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0350

Genes affected

ABCG8 (HGNC:13887): (ATP binding cassette subfamily G member 8) 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 to exclude non-cholesterol sterol entry at the intestinal level, promote excretion of cholesterol and sterols into bile, and to facilitate transport of sterols back into the intestinal lumen. It is expressed in a tissue-specific manner in the liver, intestine, and gallbladder. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG5. Mutations in this gene may contribute to sterol accumulation and atherosclerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-43846517-T-C is Benign according to our data. Variant chr2-43846517-T-C is described in ClinVar as [Benign]. Clinvar id is 1221022.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-43846517-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG8	NM_022437.3	c.322+206T>C		intron_variant		ENST00000272286.4
ABCG8	NM_001357321.2	c.322+206T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG8	ENST00000272286.4	c.322+206T>C		intron_variant		1	NM_022437.3	P1
ABCG8	ENST00000644611.1	c.334+206T>C		intron_variant
ABCG8	ENST00000643284.1	n.985T>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11759 AN: 152104 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0743

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0678

GnomAD4 exome AF: 0.0619 AC: 33907 AN: 547868 Hom.: 1186 Cov.: 7 AF XY: 0.0595 AC XY: 17149 AN XY: 288454

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.0972

Gnomad4 ASJ exome AF: 0.0989

Gnomad4 EAS exome AF: 0.0102

Gnomad4 SAS exome AF: 0.0338

Gnomad4 FIN exome AF: 0.0845

Gnomad4 NFE exome AF: 0.0611

Gnomad4 OTH exome AF: 0.0712

GnomAD4 genome AF: 0.0773 AC: 11771 AN: 152214 Hom.: 573 Cov.: 32 AF XY: 0.0770 AC XY: 5731 AN XY: 74426

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0745

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.0876

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0674

Alfa AF: 0.0634 Hom.: 405

Bravo AF: 0.0817

Asia WGS AF: 0.0440 AC: 152 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	-0.91
CADD	Benign	1.7
DANN	Benign	0.30

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: rs41360247; hg19: chr2-44073656;