chr2-43874572-T-C

Position:

• chr2-43874572-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022437.3(ABCG8):​c.1488+89T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,104,180 control chromosomes in the GnomAD database, including 37,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4257 hom., cov: 31)
  • Exomes 𝑓: 0.26 (33602 hom.)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.179

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-43874572-T-C is Benign according to our data. Variant chr2-43874572-T-C is described in ClinVar as [Benign]. Clinvar id is 1229584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-43874572-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG8	NM_022437.3	c.1488+89T>C		intron_variant		ENST00000272286.4	NP_071882.1
ABCG8	NM_001357321.2	c.1485+89T>C		intron_variant			NP_001344250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG8	ENST00000272286.4	c.1488+89T>C		intron_variant		1	NM_022437.3	ENSP00000272286	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34679 AN: 151834 Hom.: 4254 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0178

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.257 AC: 244731 AN: 952228 Hom.: 33602 AF XY: 0.260 AC XY: 128776 AN XY: 495606

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.0133

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.228 AC: 34698 AN: 151952 Hom.: 4257 Cov.: 31 AF XY: 0.228 AC XY: 16963 AN XY: 74250

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.0182

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.228

Alfa AF: 0.187 Hom.: 601

Bravo AF: 0.219

Asia WGS AF: 0.131 AC: 457 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.69

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: rs13405698; hg19: chr2-44101711;