rs12271907

Variant names:

• chr11-119156981-C-T
• rs12271907
• NM_022169.5:c.1035C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119156981-C-T
• chr11-119156981-C-A
• chr11-119156981-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_022169.5(ABCG4):​c.1035C>T​(p.Asn345Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,612,868 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (50 hom.)
• Consequence: ABCG4 NM_022169.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.901
• Publications: 7 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=-0.78).
• BP6: Variant 11-119156981-C-T is Benign according to our data. Variant chr11-119156981-C-T is described in ClinVar as Benign. ClinVar VariationId is 778564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.901 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0149 (2262/152128) while in subpopulation AFR AF = 0.0494 (2048/41424). AF 95% confidence interval is 0.0477. There are 60 homozygotes in GnomAd4. There are 1053 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 60 gene

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.1035C>T	p.Asn345Asn	synonymous	Exon 9 of 15	NP_071452.2
	ABCG4	NM_001142505.1		c.1035C>T	p.Asn345Asn	synonymous	Exon 9 of 15	NP_001135977.1	Q9H172-1
	ABCG4	NM_001348191.2		c.1035C>T	p.Asn345Asn	synonymous	Exon 9 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.1035C>T	p.Asn345Asn	synonymous	Exon 9 of 15	ENSP00000481728.1	Q9H172-1
	ABCG4	ENST00000622721.1	TSL:1	c.1035C>T	p.Asn345Asn	synonymous	Exon 8 of 14	ENSP00000484289.1	Q9H172-1
	ABCG4	ENST00000533694.5	TSL:1	n.1948C>T		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 152010 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00400 AC: 1001 AN: 249952 AF XY: 0.00320

Gnomad AFR exome AF: 0.0495

Gnomad AMR exome AF: 0.00329

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000487

Gnomad OTH exome AF: 0.00395

GnomAD4 exome AF: 0.00184 AC: 2682 AN: 1460740 Hom.: 50 Cov.: 31 AF XY: 0.00166 AC XY: 1206 AN XY: 726688

African (AFR) AF: 0.0506 AC: 1694 AN: 33450

American (AMR) AF: 0.00447 AC: 199 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.000154 AC: 4 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86100

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53400

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5760

European-Non Finnish (NFE) AF: 0.000469 AC: 521 AN: 1111446

Other (OTH) AF: 0.00388 AC: 234 AN: 60322

GnomAD4 genome AF: 0.0149 AC: 2262 AN: 152128 Hom.: 60 Cov.: 32 AF XY: 0.0142 AC XY: 1053 AN XY: 74382

African (AFR) AF: 0.0494 AC: 2048 AN: 41424

American (AMR) AF: 0.0102 AC: 156 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68012

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.000282 Hom.: 37

EpiCase AF: 0.000545

EpiControl AF: 0.000652

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	-0.78
CADD	Benign	0.22
DANN	Benign	0.72
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12271907; hg19: chr11-119027691;