rs56145149

Variant names:

• chr21-42276889-C-T
• rs56145149
• NM_016818.3:c.538-6C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_016818.3(ABCG1):​c.538-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,613,966 control chromosomes in the GnomAD database, including 3,295 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.040 (233 hom., cov: 32)
  • Exomes 𝑓: 0.051 (3062 hom.)
• Consequence: ABCG1 NM_016818.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002556
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.636
• Publications: 6 publications found

Genes affected

ABCG1 (HGNC:73): (ATP binding cassette subfamily G member 1) 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. It is involved in macrophage cholesterol and phospholipids transport, and may regulate cellular lipid homeostasis in other cell types. Six alternative splice variants have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 21-42276889-C-T is Benign according to our data. Variant chr21-42276889-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056609.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	NM_016818.3	MANE Select	c.538-6C>T		splice_region intron	N/A	NP_058198.2
	ABCG1	NM_004915.4		c.538-6C>T		splice_region intron	N/A	NP_004906.3
	ABCG1	NM_207174.1		c.571-6C>T		splice_region intron	N/A	NP_997057.1	P45844-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.538-6C>T		splice_region intron	N/A	ENSP00000381467.3	P45844-4
	ABCG1	ENST00000398437.1	TSL:1	c.976-6C>T		splice_region intron	N/A	ENSP00000381464.1	E9PGV9
	ABCG1	ENST00000361802.7	TSL:1	c.538-6C>T		splice_region intron	N/A	ENSP00000354995.2	P45844-1

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6142 AN: 152214 Hom.: 232 Cov.: 32

Gnomad AFR AF: 0.00854

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.0421

GnomAD2 exomes AF: 0.0643 AC: 16171 AN: 251430 AF XY: 0.0709

Gnomad AFR exome AF: 0.00689

Gnomad AMR exome AF: 0.0483

Gnomad ASJ exome AF: 0.0713

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.0268

Gnomad NFE exome AF: 0.0462

Gnomad OTH exome AF: 0.0668

GnomAD4 exome AF: 0.0514 AC: 75121 AN: 1461634 Hom.: 3062 Cov.: 31 AF XY: 0.0556 AC XY: 40391 AN XY: 727110

African (AFR) AF: 0.00809 AC: 271 AN: 33480

American (AMR) AF: 0.0469 AC: 2099 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 1854 AN: 26130

East Asian (EAS) AF: 0.0858 AC: 3405 AN: 39698

South Asian (SAS) AF: 0.172 AC: 14821 AN: 86228

European-Finnish (FIN) AF: 0.0298 AC: 1590 AN: 53414

Middle Eastern (MID) AF: 0.122 AC: 700 AN: 5760

European-Non Finnish (NFE) AF: 0.0421 AC: 46772 AN: 1111822

Other (OTH) AF: 0.0598 AC: 3609 AN: 60382

GnomAD4 genome AF: 0.0403 AC: 6145 AN: 152332 Hom.: 233 Cov.: 32 AF XY: 0.0435 AC XY: 3244 AN XY: 74490

African (AFR) AF: 0.00851 AC: 354 AN: 41580

American (AMR) AF: 0.0432 AC: 661 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3470

East Asian (EAS) AF: 0.101 AC: 524 AN: 5186

South Asian (SAS) AF: 0.188 AC: 907 AN: 4814

European-Finnish (FIN) AF: 0.0266 AC: 283 AN: 10624

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0444 AC: 3024 AN: 68036

Other (OTH) AF: 0.0412 AC: 87 AN: 2114

Alfa AF: 0.0384 Hom.: 123

Bravo AF: 0.0381

Asia WGS AF: 0.114 AC: 395 AN: 3478

EpiCase AF: 0.0516

EpiControl AF: 0.0543

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ABCG1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.1
DANN	Uncertain	0.98
PhyloP100		0.64
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00026
dbscSNV1_RF	Benign	0.022
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

Other links and lift over

dbSNP: rs56145149; hg19: chr21-43696999; COSMIC: COSV59202058;