chr11-119154569-G-A

Variant names:

• chr11-119154569-G-A
• rs12277959
• NM_022169.5:c.534G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022169.5(ABCG4):​c.534G>A​(p.Lys178Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,613,394 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (161 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (187 hom.)
• Consequence: ABCG4 NM_022169.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.883
• Publications: 1 publications found

Genes affected

ABCG4 (HGNC:13884): (ATP binding cassette subfamily G member 4) The protein encoded by this gene is a member of the ATP-binding cassette (ABC) transporter superfamily. 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). The encoded protein is a member of the White subfamily and plays an important role in cellular cholesterol homeostasis. This protein functions as either a homodimer or as a heterodimer with another ABC subfamily protein such as ABCG1. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-119154569-G-A is Benign according to our data. Variant chr11-119154569-G-A is described in ClinVar as Benign. ClinVar VariationId is 773016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.883 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022169.5. 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
	ABCG4	NM_022169.5	MANE Select	c.534G>A	p.Lys178Lys	synonymous	Exon 5 of 15	NP_071452.2
	ABCG4	NM_001142505.1		c.534G>A	p.Lys178Lys	synonymous	Exon 5 of 15	NP_001135977.1	Q9H172-1
	ABCG4	NM_001348191.2		c.534G>A	p.Lys178Lys	synonymous	Exon 5 of 15	NP_001335120.1	Q9H172-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG4	ENST00000619701.5	TSL:1 MANE Select	c.534G>A	p.Lys178Lys	synonymous	Exon 5 of 15	ENSP00000481728.1	Q9H172-1
	ABCG4	ENST00000622721.1	TSL:1	c.534G>A	p.Lys178Lys	synonymous	Exon 4 of 14	ENSP00000484289.1	Q9H172-1
	ABCG4	ENST00000533694.5	TSL:1	n.1447G>A		non_coding_transcript_exon	Exon 3 of 10

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3790 AN: 152264 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00657 AC: 1644 AN: 250188 AF XY: 0.00501

Gnomad AFR exome AF: 0.0889

Gnomad AMR exome AF: 0.00494

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00274 AC: 4005 AN: 1461012 Hom.: 187 Cov.: 32 AF XY: 0.00240 AC XY: 1742 AN XY: 726816

African (AFR) AF: 0.0961 AC: 3210 AN: 33396

American (AMR) AF: 0.00542 AC: 241 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00504 AC: 29 AN: 5756

European-Non Finnish (NFE) AF: 0.0000792 AC: 88 AN: 1111736

Other (OTH) AF: 0.00688 AC: 415 AN: 60348

GnomAD4 genome AF: 0.0250 AC: 3807 AN: 152382 Hom.: 161 Cov.: 33 AF XY: 0.0247 AC XY: 1843 AN XY: 74524

African (AFR) AF: 0.0855 AC: 3555 AN: 41586

American (AMR) AF: 0.0118 AC: 180 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68042

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0104 Hom.: 185

Bravo AF: 0.0296

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.3
DANN	Benign	0.64
PhyloP100		0.88
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12277959; hg19: chr11-119025279;