rs896751158

Variant names:

• chr11-119150029-G-T
• rs896751158
• NM_022169.5:c.64G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119150029-G-T
• chr11-119150029-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001348192.2(ABCG4):​c.-175G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ABCG4 NM_001348192.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16530377).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348192.2. 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.64G>T	p.Val22Leu	missense	Exon 2 of 15	NP_071452.2
	ABCG4	NM_001348192.2		c.-175G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 16	NP_001335121.1	Q9H172-2
	ABCG4	NM_001142505.1		c.64G>T	p.Val22Leu	missense	Exon 2 of 15	NP_001135977.1	Q9H172-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG4	ENST00000619701.5	TSL:1 MANE Select	c.64G>T	p.Val22Leu	missense	Exon 2 of 15	ENSP00000481728.1	Q9H172-1
	ABCG4	ENST00000622721.1	TSL:1	c.64G>T	p.Val22Leu	missense	Exon 1 of 14	ENSP00000484289.1	Q9H172-1
	ABCG4	ENST00000615496.4	TSL:2	c.64G>T	p.Val22Leu	missense	Exon 2 of 15	ENSP00000479253.1	Q9H172-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250198 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460938 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726836

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.23	N
PhyloP100		1.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.048
Sift	Benign	0.080	T
Sift4G	Benign	0.14	T
Polyphen		0.025	B
Vest4		0.18
MutPred		0.35		Loss of catalytic residue at V22 (P = 0.0882)
MVP		0.59
ClinPred		0.18	T
GERP RS		3.9
PromoterAI		0.0043	Neutral
Varity_R		0.14
gMVP		0.30
Mutation Taster		=85/15	polymorphism

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: rs896751158; hg19: chr11-119020739;