16-11826180-A-G

Position:

• chr16-11826180-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_131216.1(BCAR4):​n.134+2519T>C variant causes a intron, non coding transcript 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 NR_131216.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAR4	NR_131216.1	n.134+2519T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAR4	ENST00000571158.5	n.217+2142T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.702

Alfa AF: 0.639 Hom.: 12332

Bravo AF: 0.695

Asia WGS AF: 0.550 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4561483; hg19: chr16-11920037;