16-11826180-A-G

Variant names:

• chr16-11826180-A-G
• rs4561483
• ENST00000571158.6:n.240+2142T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000571259.6(BCAR4):​n.331+2142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,916 control chromosomes in the GnomAD database, including 35,193 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35193 hom., cov: 32)
• Consequence: BCAR4 ENST00000571259.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 11 publications found

Genes affected

BCAR4 (HGNC:22170): (breast cancer anti-estrogen resistance 4) This gene produces a spliced long non-coding RNA (lncRNA) that has been implicated in breast cancer metastasis. It was originally identified in a screen for genes responsible for the development of resistance to anti-estrogens in breast cancer cells. It is thought that release of CCL21 enables this lncRNA to bind to the SNIP1 and PNUTS transcription factors, thereby activating a non-canonical GLI-dependent hedgehog signaling pathway that promotes cancer cell migration and invasion. A similar gene in cow expresses a protein in mature oocytes and preimplantation embryos. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Apr 2015]

ENSG00000294735 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000571259.6. 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
	BCAR4	NR_024049.1		n.512-1441T>C		intron	N/A
	BCAR4	NR_024050.1		n.204+2142T>C		intron	N/A
	BCAR4	NR_131216.1		n.134+2519T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAR4	ENST00000571158.6	TSL:5	n.240+2142T>C		intron	N/A
	BCAR4	ENST00000571259.6	TSL:2	n.331+2142T>C		intron	N/A
	BCAR4	ENST00000573037.2	TSL:3	n.520+2142T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102647 AN: 151798 Hom.: 35171 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.706

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.676 AC: 102722 AN: 151916 Hom.: 35193 Cov.: 32 AF XY: 0.674 AC XY: 49998 AN XY: 74224

African (AFR) AF: 0.743 AC: 30809 AN: 41456

American (AMR) AF: 0.765 AC: 11662 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2460 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2056 AN: 5172

South Asian (SAS) AF: 0.581 AC: 2805 AN: 4826

European-Finnish (FIN) AF: 0.607 AC: 6377 AN: 10502

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44324 AN: 67946

Other (OTH) AF: 0.702 AC: 1476 AN: 2102

Alfa AF: 0.644 Hom.: 14246

Bravo AF: 0.695

Asia WGS AF: 0.550 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-0.071

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4561483;

hg19: chr16-11920037;